Clues for the differential diagnosis of hypersensitivity pneumonitis as an expectant variant of diffuse parenchymal lung disease.

Hypersensitivity pneumonitis, also called extrinsic allergic alveolitis, a type of diffuse parenchymal lung disease (DPLD), is an immunologically mediated pulmonary disease induced by inhalation of various antigens. As data on the frequency of hypersensitivity pneumonitis are lacking in Turkey, a retrospective analyses was performed in 43 patients with DPLD, followed up over seven years. The objective was to discover cases fulfilling the diagnostic criteria for hypersensitivity pneumonitis, to determine the frequency and/or the new characteristics of the disease, and to pick up clues for differentiating it from other DPLDs. The four subjects with hypersensitivity pneumonitis (9%) who lived in an urban area were studied in detail. The most common symptoms were dry cough and dyspnoea. According to the symptom duration, clinical features, radiological and pathological findings, three were diagnosed with chronic and one with subacute hypersensitivity pneumonitis. Patients with hypersensitivity pneumonitis and those with DPLD were compared by means of age, sex, smoking status, symptom duration, haematology, erythrocyte sedimentation rate, peripheral cell count, spirometric parameters, blood gases, and diffusion capacity. No statistically significant difference was detected in these parameters except for forced expiratory volume in one second (FEV(1)) and forced vital capacity (FVC). In conclusion, patients with a history of antigen exposure, with mild symptoms such as dry cough and dyspnoea, and who have diffuse interstitial lung involvement on radiology should be carefully evaluated for hypersensitivity pneumonitis. Moreover, among other DPLDs, stable FEV(1) or FVC values may be the clues for establishing the diagnosis of hypersensitivity pneumonitis. However, further studies are needed in larger series of patients.

Cellular profile of bronchoalveolar lavage fluid in Turkish miners.

Pneumoconiosis is still a health problem in Turkey and has a relatively high incidence. Retired underground miners were investigated to document alveolitis, and to observe the difference in the cellular profiles of bronchoalveolar lavage (BAL) fluid with or without pneumoconiosis. Twenty nine retired male miners and 17 controls, eight non-smokers (four male, four female) and nine smokers (six male, three female), without any dust exposure were evaluated. According to the International Labor Office 1980 classification system, the miners were allocated to three subgroups: eight without pneumoconiosis, 11 with simple pneumoconiosis, and 10 with progressive massive fibrosis (PMF). Spirometric tests and arterial blood gases analysis were done and fibreoptic bronchoscopy and BAL were performed in all subjects. The study and the control subjects were comparable in respect to age, smoking habits, except the non-smoker controls, and the duration of dust exposure, except the controls. The amount of recovered BAL fluid was lower in all miners compared with the non-smoker controls (p<0.05). The amount of recovered BAL fluid and the total cell count correlated significantly (r = 0.48, p<0.01). The percentage of lymphocytes in the BAL fluid of miners without pneumoconiosis and with PMF (p<0.05) and that of simple pneumoconiosis (p<0.01) was significantly lower compared with the non-smoker controls. Alveolitis was not a representative feature of Turkish subjects with an occupational history of underground mining, and BAL fluid cellular profile did not seem to be different in miners with or without pneumoconiosis.

Adenosine deaminase activity in bronchoalveolar lavage in Turkish patients with smear negative pulmonary tuberculosis.

The sputum smear-negative patients have been a diagnostic challenge for health professionals. Adenosine deaminase (ADA) activity has been shown to rise in various body fluids of patients with tuberculosis (Tb). A prospective clinical trial was conducted to determine the diagnostic value of ADA activity in bronchoalveolar lavage (BAL) in sputum smear-negative subjects highly suggestive for pulmonary Tb. Nineteen (M/F: 15/4, mean age 46.8 +/- 16.5 years) sputum smear-negative patients highly suggestive for pulmonary Tb constituted Group I. Acid fast bacilli (AFB) grew on sputum and/or BAL culture of all subjects in this group. Twenty-nine patients (M/F: 19/10, mean age 55.7 +/- 8.0 years) with non-tuberculous pulmonary diseases constituted Group II. Ten of them had interstitial lung disease, nine lung cancer, five pneumonia and five COPD. Twelve subjects (M/F: 7/5, mean age 48.4 +/- 12.8 years) constituted the controls (Group III) undergoing fiberoptic bronchoscopy (FOB) for various indications and the lungs were found to be normal eventually. Albumin and ADA activity levels were measured in plasma and BAL in all the subjects. LocalADA was calculated. PlasmaADA and BALADA of Group I was significantly higher (P < 0.001) than that of the other groups. LocalADA was also the highest in Group I when compared with the others (P < 0.001) but that of Group II was also higher (P < 0.01) when compared with controls. With a cut-off value derived from the control subjects, sensitivity of BALADA was 100% and specificity 85.3%. Sputum PCR results are available in a couple of days whereas that of BALADA are available in a couple of hours and BALADA costs cheaper than PCR in our country. Therefore, we conclude that BALADA may be a useful, cheaper and faster diagnostic test in sputum smear-negative patients highly suggestive for pulmonary Tb. LocalADA need not be calculated as it is also significantly higher in Group II subjects and thus not as reliable as BALADA.

Chlamydia pneumoniae infection and acute exacerbation of chronic obstructive pulmonary disease (COPD).

The objective of the study was to investigate the possible association of Chlamydia pneumoniae (Cpn) in acute exacerbations of chronic obstructive pulmonary disease (COPD) patients. Thirty-eight acutely exacerbated COPD patients and 17 healthy smokers were enrolled in the study, as the study and control groups respectively. Nasopharyngeal swabs and paired serum samples for antibody testing of Cpn (microimmunofluorescence--MIF) were obtained from all subjects. Sputum cultures of COPD patients were also performed. No pathogenic bacteria were isolated from nasopharyngeal swabs in any subject. Serologic evidence of recent Cpn infection was observed in 13 (34%) COPD patients and in one (5%) control subject. The prevalence of Cpn IgG and IgM antibodies representing acute infection were significantly higher in COPD patients than in control subjects (P < 0.05 and P < 0.01 respectively). Prevalence of IgA antibodies and IgG pre-existing antibodies did not show any difference (P > 0.05). Microbiologic culture of the sputa yielded potentially pathogenic micro-organisms in 23 of 38 (60%) COPD patients. Alpha-haemolytic streptococcus (35%), Niesseria spp. (31%) and Candida spp. (9.5%) were most prominent micro-organisms in positive cultures. Although a high prevalence of IgG antibodies against Cpn was detected, it was the sole causative agent in only four (10%) patients. We conclude that a remarkable number of COPD patients (34%) are acutely infected with Cpn and it may either be the sole causative agent or frequently a co-agent in acute exacerbations.

Evaluation of Cyfra 21-1: a potential tumor marker for non-small cell lung carcinomas.

Cyfra 21-1 is a tumor marker based on the determination of water-soluble cytokeratin 19 which is secreted by normal or malignantly transformed epithelial cells. It is suggested to be a valuable marker in patients with non-small cell lung carcinoma (NSCLC). A prospective clinical study was conducted to investigate the value of Cyfra 21-1 for diagnosis, determination of subtypes, staging, and evaluation of therapy response in patients with lung carcinoma (Ca). Sixty-nine patients (mean age: 60.9 +/- 9.2 years, M/F:12.8) treated between 1994 and 1998 inclusive, and 13 healthy smokers (mean age:50.9 +/- 4.8 years, M/F:1.6) constituted the study group and control group, respectively. Venous blood samples (10 ml) were obtained from all subjects. Posttreatment blood samples were also obtained from 14 NSCLC patients. Cyfra 21-1 levels (cutoff value 3.3 ng/ml) were determined by ELSA-Cyfra 21-1 kit (CIS bio international, France) through immunoradiometric assay (IRMA). Cyfra 21-1 levels did not differ between smoking and non-smoking subjects within each group (p > 0.05). Cyfra 21-1 was significantly elevated in lung Ca cases irrespective of the cell type (p < 0.05). It was significantly elevated in squamous cell and adenocarcinoma varieties with the most prominent elevation in squamous cell type (p < 0.05). In lung Ca, the specificity and sensitivity of Cyfra 21-1 was 92.3% and 52.2%, respectively. Sensitivity was 65.5% for NSCLC, 70.5% for squamous cell, and 45.5% for adenocarcinoma varieties, with highest sensitivity rates in Stage IIIA + IIIB (87.5%) and Stage IV (75%) of squamous cell lung Ca. Cyfra 21-1 level was significantly decreased after treatment in NSCLC patients (n 14) (p < 0.01). Cyfra 21-1 is a tumor marker that helps to establish the diagnosis and differentiation of cell type and evaluation of response to therapy in patients with NSCLC.

Neurophysiological changes in COPD patients with chronic respiratory insufficiency.

Chronic hypoxemia is known to cause peripheral neuropathy (PNP) in chronic obstructive pulmonary disease (COPD) patients. We aimed to know how often PNP is encountered in such patients and the changes in the central nervous system (CNS) if any. We enrolled 32 patients (30 M, 2 F; mean age +/- SD: 61.5 +/- 8.8 years) with COPD into the study. PaO2 > or = 55 mmHg was considered as the cut-off value designating tissue hypoxia. According to this cut-off value the subjects were divided into two groups: Group I, n: 19, PaO2 < 55 mmHg and Group II, n: 13, PaO2 > or = 55 mmHg. All subjects were evaluated with motor and sensory nerve conduction studies (MNCV and SNCV, respectively), electromyography, visual and brainstem evoked potentials (VER and BAER, respectively). We detected PNP in 93.8% of the study subjects. Distal latency of sural nerve correlated significantly with cigarette consumption and reduction in PEFR. SNCV of median nerve was reduced as PaCO2 was elevated and pH was lowered. BAER wave III latency showed significant inverse correlation with PEFR, FEF25 and FEF25-75. Interpeak latency (IPL) of BAER I-III was also significantly and inversely correlated with FEV1/FVC and FEF25-75. IPL of BAER III-V too showed significant correlations with PaCO2, HCO3- and pH of the arterial blood. As BAER III and IPLs of it represent the pontomedullary portion of the brain, cigarette smoking and airways obstruction may not only cause peripheral neuropathy but also a delay in evoked responses of the brain stem by inducing chronic hypercapnia and respiratory acidosis in patients with COPD.

Pharmaceutical industry agenda setting in mental health policies.

The development of political agenda-setting through the use of sophisticated public relations techniques is threatening to undermine the delicate balance of representative democracy. This has important ramifications for policies aimed at providing mental health services and the implementation of mental health laws. The principal agenda setters in this area are pharmaceutical companies with commercial reasons to promote public policies that expand the sales of their products. They have manufactured highly effective advocacy coalitions that incorporate front groups in order to set the policy agenda for mental health. However, policies tailored to their commercial purpose are not necessarily beneficial either for patients or the society at large.

Formoterol and salmeterol in partially reversible chronic obstructive pulmonary disease: A crossover, placebo-controlled comparison of onset and duration of action.

BACKGROUND: In contrast to the well-known activity profile in asthma, the precise efficacy and optimum dose schedules of long-acting beta(2)-agonists in chronic obstructive pulmonary disease (COPD) are not clear. OBJECTIVE: In this study, we aimed to compare the onset and the duration of action of a single inhalation of formoterol and salmeterol in COPD patients having partially reversible airway obstruction. METHODS: In a double-blind, randomized, crossover and placebo-controlled study design, the respiratory functions of 22 patients (mean age 57.3+/-5.4 years) having mild to severe COPD (5 mild, 8 moderate and 9 severe) and partially reversible airway obstruction [mean baseline reversibility of forced expiratory volume in 1 s (FEV(1)) 19.3+/-3.1%] were evaluated after inhalation of 12 microg formoterol and 50 microg salmeterol. RESULTS: Regarding the onset of bronchodilator action, the mean absolute increase of 0.20 liters in FEV(1) 10 min after inhalation of formoterol was significantly higher than baseline and that of placebo (0.04 liters), whereas that of salmeterol (0.11 liters) did not reach statistical significance. At 20 min, both formoterol (0.25 liters) and salmeterol (0.20 liters) produced a significant increase in FEV(1) compared with baseline and with that of placebo (0.04 liters). The peak bronchodilator effects occurring at 60 and 120 min following formoterol (0.39 liters) and salmeterol (0.40 liters) inhalation, respectively, were significantly higher than the corresponding levels of placebo (0.02 and -0.12 liters, respectively). Concerning the duration of action, the 12-hour values of both formoterol (0.25 liters) and salmeterol (0.22 liters) were significantly higher than that of placebo (-0.12 liters). The area under the curve values of FEV(1) of formoterol (3.5+/-1.3 l.h) and salmeterol (3.2+/-1.2 l x h) averaged over 12 h were comparable and higher than placebo values (1.2+/-0.5 l x h). After formoterol inhalation 2 patients experienced tremor and 1 had palpitation; 1 tremor and 1 headache attack were noted after salmeterol. For the pharmacologically predictable side effects, there was no difference between the drugs. CONCLUSIONS: In conclusion, this study revealed that a single dose of 12 microg formoterol and 50 microg salmeterol provided comparable bronchodilation within 12 h and had tolerable side effects in patients with mild to severe COPD having partially reversible airway obstruction.

Time course of myocardial amiodarone uptake in the piglet heart using a chronic animal model.

This investigation sought to study single dose pharmacokinetics of amiodarone in a chronic animal model. We developed a new chronic animal model that allows serial direct access to the heart of the immature piglet via an implanted acrylic thoracic window. Following instrumentation and 72-hour recovery, amiodarone (5 mg/kg) was administered as a single intravenous bolus in immature piglets. Timed paired serum samples and myocardial biopsies for amiodarone level were obtained prior to, and up to 72 hours following, amiodarone administration. Peak concentrations of amiodarone in both serum (3.60 +/- 1.02 micrograms/ml) and tissue (84.2 +/- 6.50 ng/mg) occurred within 5 minutes of drug administration. As reported by others, this study demonstrated that the volume of distribution (VD) of amiodarone was large (33.31 +/- 35.21 L/kg), and the clearance (Cl) was low (13.6 +/- 4.4 ml/min/kg). Marked prolongation of both the serum t1/2 (29.98 +/- 29.26 hours) and the myocardial t1/2 (29.20 +/- 29.49 hours) were noted as well. The early, rapid myocardial peak of amiodarone in the immature myocardium corresponds with recent clinical observations of onset of antiarrhythmic efficacy 5 to 10 minutes following intravenous amiodarone administration in young children.

Endoscopic scoring system in patients with allergic rhinitis.

Visual inspection of the airways in patients with chronic bronchitis and asthma by fiberoptic bronchoscopy and the relation of these findings to bronchoalveolar lavage (BAL) fluid analysis or some clinical parameters have been reported previously. In this study, we have attempted to assess and grade airway inflammation in allergic rhinitis patients (ARP) by fiberoptic bronchoscopy. During the procedure, BAL was obtained and visual inspection of airways done by the method used by Thompson et al. Ten ARP with bronchial hyperreactivity (BHR) (Group 1), 10 ARP without BHR (Group 2) and 2 nonatopic, healthy subjects (Control Group) were studied. The fluid recovery and differential cell concentration were similar in the three groups. The inflammatory scores were 11.0 +/- 7.0, 13.8 +/- 6.9, 15.0 +/- 4.2 in group 1, group 2 and control group, respectively, without showing any significant differences between the groups. There was no correlation between the inflammatory score and PC20 to methacholine. This indicates that BHR in ARP will need explanations other than the inflammation within airways.

Precipitous exit block with epicardial steroid-eluting leads.

Between January 1990 and October 1992, we implanted 16 steroid-eluting ventricular epicardial pacing leads (Medtronic 10295A and 10295B/4965) in 12 patients. There were 8 males and 4 females ranging in age from 3 months to 49 years (mean 8.7 +/- 13.2, median 6.0 years). Structural cardiac disease was present in 11 of 12 patients. Follow-up ranged from 3-73 months postimplant (mean 35.7 +/- 22.3, median 28.5 months). Lead fracture (10295A) occurred in 1 of 12 patients. Of the remaining 11 patients, 8 of 11 have very low long-term pacing thresholds. Unexpectedly, 3 patients demonstrated precipitous threshold increases from 3 months to 3.5 years postimplant. Although no deaths resulted in these exit block patients, 1 of 3 exit block patients developed marked worsening of congestive heart failure. We reviewed and analyzed the data obtained at 4 weeks postimplant for all of the 10295A and 4965 patients in the entire Medtronic clinical study database. Using the criterion of a 4 week postimplant pacing threshold > or = 0.12 ms (5 V), we found that the long-term risk of eventual exit block was 27.3% for the 10295A lead (P = 0.005) and 7.5% for the 10295B/4965 lead (P = 0.03). We, therefore, recommend that in patients implanted with the 4965 steroid-eluting epicardial lead, ventricular pacing thresholds > or = 0.12 ms (5 V) measured at 4 weeks postimplant should prompt frequent threshold testing to detect late and potentially sudden ventricular pacing threshold increases.

Light and electron microscope study in allergic rhinitis patients (ARP) with or without bronchial hyperreactivity (BHR).

Little is known about the pathogenesis of bronchial hyperreactivity associated with allergic rhinitis. For this purpose, bronchial biopsies and bronchoalveolar lavage from 6 allergic rhinitis patients with bronchial hyperreactivity, 5 allergic rhinitis patients without bronchial hyperreactivity and 3 healthy, normoreactive control subjects were obtained by fiberoptic bronchoscope and investigated with light and transmission electron microscope. Varying degrees of morphological alterations were observed in all groups; however, the intensity of the epithelial shedding, goblet cells, basement membrane thickness, stromal collagenous fibers and smooth muscle cells appeared to be increased in allergic rhinitis patients with bronchial hyperreactivity. In the mucosa and submucosa, the numbers and activation of lymphocytes, neutrophils and macrophages were lower in allergic rhinitis patients with bronchial hyperreactivity than in the control group and in allergic rhinitis patients without bronchial hyperreactivity. In accordance with these findings, bronchoalveolar lavage showed increased numbers of lymphocytes and surface alterations of phagocytic cells in allergic rhinitis patients without bronchial hyperreactivity. As a result, we could not find evidence of inflammation accompanying bronchial hyperreactivity in allergic rhinitis patients.

The mechanism of bronchial hyperreactivity in allergic rhinitis patients. A light microscopic study on BAL and bronchial biopsy.

Epidemiological data indicated that allergic rhinitis often coexists with and may precede the development of reactive airway disease. In particular, ARP with BHR are more likely to develop asthma. However, the pathogenesis of BHR associated with allergic rhinitis is still remains uncertain. Therefore we designed the study on ARP with/without BHR. The aim of this study were to investigate the presence of an inflammatory process in lower respiratory tract in ARP and to relate these changes to airway responsiveness Eleven ARP with BHR (Group I), eleven ARP without BHR (Group II) and two control patients (Control group) were studied. All of the ARP were judged atopic on the basis of positive skin prick test to common inhalant allergens. Bronchial challenges were performed with increasing concentration of M. All the subjects underwent fiberoptic bronchoscopy, BAL and bronchial biopsies were obtained for pathologic examination. The mean total cell and the mean percentage of macrophages, lymphocytes, neutrophils and eosinophils in BAL fluid were in normal range in all groups without any significant differences between the groups. There weren't any correlation between PC20 to M and the total cell counts and percentage counts of these cells. In bronchial biopsy samples, the absolute numbers of lymphocytes, neutrophils, eosinophils and mast cells in the submucosa showed no differences between the three groups. The epithelial shedding was more extensive in ARP than control subjects (p = 0.05). The thickness of the epithelium was prominent in Group I (p < 0.05) but there was no significant differences in the basement membrane thickening between the three groups. We could only find an inverse correlation between PC20 to M and the mast cell counts in the submucosa (r xy:-0.815 p < 0.05). In conclusion, we couldn't observe any prominent morphological changes which indicate that may cause of BHR in ARP except the increased epithelial shedding in Group I. However, the increased epithelial shedding is not a reliable criterion to comment because of the possibility of mechanical damage of bronchial biopsies caused by the forceps.

Clinical features of the yellow nail syndrome.

The yellow nail syndrome is a rare cause of exudative pleural effusions. Diagnosis is based on the presence of typical clinical features, striking nail changes, lymphedema, and pleural effusions of undetermined etiology. There is no direct relationship between the syndrome and primary immunologic disorders, malignancies, endocrine abnormalities, or connective tissue diseases. In patients with symptomatic pleural effusions, pleurodesis is beneficial but no treatment for the nail changes has been devised.

Ventricular arrhythmias in postoperative tetralogy of Fallot.

Ventricular arrhythmias in patients after total surgical repair of tetralogy of Fallot have been associated with late sudden death. In this large multicenter retrospective study of 359 patients with postoperative tetralogy of Fallot, spontaneous ventricular premature complexes (VPCs) on 24-hour ambulatory electrocardiographic monitoring and laboratory-induced ventricular tachycardia (VT) by electrophysiologic stimulation were analyzed. The mean age at surgical repair was 5 years and the mean follow-up duration after repair was 7 years. Spontaneous VPCs on ambulatory monitoring were found in 48% and induced VT on electrophysiologic stimulation was found in 17% of patients. Both spontaneous VPCs and induced VT were significantly related to delayed age at repair, longer follow-up interval, symptoms of syncope or presyncope and right ventricular systolic hypertension (greater than 60 mm Hg) (p less than 0.05), but not to right ventricular diastolic pressure greater than 8 mm Hg. The VPCs on ambulatory monitoring were more complex with increasing age at repair and follow-up duration. Induction of VT on electrophysiologic stimulation correlated with spontaneous VPCs including VT on 24-hour ambulatory electrocardiographic monitoring. The electrophysiologic stimulation protocol varied and the induction of VT increased with a more aggressive stimulation protocol. While induced sustained monomorphic VT was related to all forms of spontaneous VPCs, induced nonsustained polymorphic VT was related to more complex forms of VPCs on ambulatory monitoring. VT was not induced in asymptomatic patients who had normal 24-hour ambulatory electrocardiographic monitoring and normal right ventricular systolic pressure. (ABSTRACT TRUNCATED AT 250 WORDS)

Aneurysms of aberrant right subclavian artery: a rare cause of the superior vena cava syndrome.

Aneurysms of an aberrant right subclavian artery are very rare. Since 1956, only 36 cases have been reported in the literature. 2 cases of aneurysms of an aberrant right subclavian artery are presented. The patients were admitted with the symptoms of a superior vena cava syndrome. During the radiographic examination, the presence of superior mediastinal masses was noticed. The aneurysms were resected successfully. The clinical presentation, surgical management and prognosis of our two cases of aneurysms of an aberrant right subclavian artery are reported, and a review of the literature is added.

Conduction abnormalities detected by electrophysiologic testing following repair of ostium primum atrioventricular septal defect.

Since 1983 we have performed electrophysiologic studies in 6 patients who had previously undergone repair of an ostium primum atrioventricular septal defect. Information obtained during electrophysiologic studies was crucial in guiding appropriate pacemaker therapy in these patients. As judged from the resting electrocardiogram, sinus or junctional bradycardia was present in 3/6, atrial flutter / fibrillation in 2/6, and paced rhythm in 2 patients who had had ventricular pacemakers implanted for complete atrioventricular block. During maximal exercise testing 4 patients had reduced heart rates; 2 had sudden drops in heart rate at 1 min postexercise; 1 patient had exercise induced ventricular bigeminy; and 1 patient with atrial flutter and 2: 1-4: 1 block at rest developed 1: 1 conduction during Stage II with an effective ventricular rate of 220/min. During electrophysiologic studies, the maximum corrected sinus node recovery time was abnormal in five of the six, ranging from 410 to 5630 msec. There was no spontaneous atrial rhythm in the other patient. Complete atrioventricular block was present in 2 patients while the atrioventricular Wenckebach phenomenon occurred abnormally at atrial pacing cycle lengths greater than 450 msec in 2 others. Supraventricular tachycardia or atrial flutter/fibrillation, was either spontaneous or induced in 2/6 patients, while ventricular tachycardia was induced in 1/3 patients who underwent programmed ventricular stimulation. Electrophysiologic studies were important in unmasking severe sinus node disease in 3 patients and atrioventricular node disease in 2. We therefore recommend that electrophysiologic studies be strongly considered as part of the evaluation of conduction abnormalities following repair of ostium primum atrioventricular septal defect.