Echocardiography-derived septal curvature correlated with invasive hemodynamics in pediatric pulmonary hypertension.

BACKGROUND: Right ventricular function and afterload are associated with clinical outcomes in pulmonary hypertension (PH). MRI-derived interventricular septal curvature has been associated with invasive hemodynamics in PH patients. This study sought to determine the relationship of echocardiography derived septal curvature with invasive hemodynamics in pediatric PH patients. METHODS: A single center chart review identified 56 pediatric patients with PH and 50 control patients with adequate echocardiography to assess septal curvature within one month of initial cardiac catheterization. Echocardiographic indices of septal flattening including end-systolic eccentricity index (EIs), maximum EI (EImax), minimum septal curvature (SCmin), and average SC (SCavg) were determined. RESULTS: PH patients had a median right ventricular systolic pressure of 64 mmHg (interquartile range (IQR) 48-81), mean pulmonary artery pressure of 44 mmHg (IQR 32-57), pulmonary vascular resistance of 7.9 iWU (IQR 4.8-12.9), and pulmonary capillary wedge pressure of 10 mmHg (IQR 8-12). Patients with PH had higher EIs and EImax and lower SCmin and SCavg compared to control patients. SCavg demonstrated the strongest association with right ventricular systolic pressure (R2 0.73, p < 0.0001), mean pulmonary artery pressure (R2 0.63, p < 0.0001), and pulmonary vascular resistance (R2 0.47, p < 0.0001). All septal curvature indices were associated with the composite adverse outcome, including Potts shunt, lung transplantation, and death. SCmin (HR 0.29; 95%CI 0.07-0.97) and SCavg (HR 0.15; 95%CI 0.03-0.72) were the only septal flattening indices associated with death. CONCLUSIONS: Echocardiography derived septal curvature is a non-invasive marker of ventricular afterload and adverse outcomes.

Association of simian immunodeficiency virus Nef with cellular serine/threonine kinases is dispensable for the development of AIDS in rhesus macaques.

The nef gene of simian immunodeficiency virus (SIV) is essential for high viral load and induction of AIDS in rhesus monkeys. A mutant form of the SIVmac239 Nef, which contains changes in a putative SH3-binding domain (amino acids 104 and 107 have been changed from PxxP to AxxA), does not associate with cellular serine/threonine kinases, but is fully active in CD4 downregulation and associates with the cellular tyrosine kinase Src. Infection of two rhesus macaques with SIVmac239 containing the mutant AxxA-Nef caused AIDS and rapid death in both animals. No reversions were observed in the majority of nef sequences analyzed from different time points during infection and from lymphatic tissues at the time of death. Our findings indicate that the putative SH3-ligand domain in SIVmac Nef and the association with cellular serine/threonine kinases are not important for efficient replication and pathogenicity of SIVmac in rhesus macaques.

[Granular cell tumour in a patient with pulmonary tuberculosis]. / Granularzelltumor der Trachea bei einer Patientin mit offener pulmonaler Tuberkulose.

Primary tracheal tumours are rare and often only cause symptoms at a late stage, when the tumour obstructs most of the tracheal lumen. We report the case of a 45-year-old woman with pulmonary tuberculosis and a tumour in the trachea, which had been interpreted as a tuberculous lymph node perforating the tracheal wall. Bronchoscopy revealed a white, glossy, papillomatous lesion in the ventral wall of the trachea, which was identified by histology as a granular cell tumour. After culture conversion of the underlying tuberculosis, which led to the detection of the lesion, the tumour was surgically removed. Granular cell tumours rarely appear in the trachea, they may be multifocal and sometimes follow a malignant course. Complete resection is the treatment of choice and recurrence rates are low.

[Rehabilitation of lung cancer patients]. / Rehabilitation bei Patienten mit Lungenkarzinom.

In the industrial world incidence and prevalence of lung cancer are increasing. At the same time new drugs and new therapies can improve cure rates, prolong survival and procure better quality of life. Nowadays, oncology provides multimodal therapies which may cause psychological and physical stress in the often multimorbid patients. Furthermore, the tumour itself may cause pain and bring about special nutritional and coping problems. Patients may face fear and depression, nicotine withdrawal, socioeconomic problems and the risk of permanent disability. The sequelae of multimodal therapies can vary according to the chosen procedure such as surgery, radiotherapy, chemotherapy, and hormone or immune treatment. After the end of treatment, rehabilitation needs to address the never-ending fear of disease relapse, dyspnoea and suffocation feelings as well as the psychological problems associated with lung cancer. At the initiation of rehabilitation, physical performance is usually limited by the underlying disease as well as the different therapeutic modalities. In Germany, rehabilitation is mainly carried out as in-patient rehabilitation in specialised oncological or pneumological rehabilitation centres. The analysis of published data shows that in-patient rehabilitation has not been evaluated sufficiently for its efficiency so far. This also applies to out-patient rehabilitation, which is largely unavailable in Germany. Oncologists, pneumologists and patient groups agree that rehabilitation should be offered or even strongly recommended to all lung cancer patients.

Lung disease severity, chronic inflammation, iron deficiency, and erythropoietin response in adults with cystic fibrosis.

Chronic lung disorders are usually associated with a hypoxia driven increase in red cell mass. However, patients with cystic fibrosis (CF) often have normal or decreased haemoglobin levels. The present prospective observational study in cystic fibrosis patients was performed to determine which factors were involved in alterations in the hematopoetic response to corresponding arterial oxygen pressure. Sixty adult patients (age 21-51) with stable CF were included. They all had vitamin A, D, E, and K but no vitamin B12 supplementation. Twenty-five patients were on oral Fe(2+) (100 mg/day). Resting arterial blood gases, lung function, complete blood counts, parameters of iron status, CRP, sputum microbiology and serum erythropoietin were measured at recruitment and after 3 and 6 months. Patients had varying degrees of pulmonary functional impairment and 9% were hypoxemic (arterial oxygen pressure <60 mm Hg). Low-grade systemic inflammation (CRP > 0.5 mg/dl) was present in 40% of the patients, who all had bacterial colonization. None of the patient had erythrocytosis and 12 patients had anemia. There was no significant difference in iron status between patients with or without chronic iron supplementation and erythropoietin levels were normal. During the 6 months observation period no significant changes occurred. The patients exhibited an impaired erythropoietic response to hypoxemia with normal or low hematocrit in spite of chronic lung disease which might be caused by chronic inflammation associated with CF. Linear multivariate regression analysis revealed CRP levels but neither iron substitution, nor erythropoietin levels nor lung function parameters as independent determinant of haemoglobin levels. CF may be associated with anemia of variable severity as expression of the chronic inflammation present in these patients. The therapeutic consequences are to treat the underlying inflammation rather than to supplement iron.

Monitoring of expiratory flow rates and lung volumes during a high altitude expedition.

BACKGROUND: Data on lung volumes and changes in flow-volume spirometry at high altitude are few and do not provide comprehensive assessment of the occurring changes. This study characterizes alterations of the forced expiratory flow-volume curve (FEFV-curve) and lung volumes at increasing altitude. METHODS: FEFV-curve and lung volumes at increasing altitude were characterized by daily assessment of peak expiratory flow (PEF), forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and maximal expiratory flow rates (MEF 25, 50, 75) at 25%, 50% and 75% of the FEFV-curve with a portable spirometer (turbinometric method) three times a day during an expedition to Mustagh Ata (7545m) in 15 healthy mountaineers. RESULTS: With increasing altitude FVC and FEV1 were reduced by up to 25% (74.8% / 74.6% of baseline) and MEF25 was reduced to 81.5% of baseline values. PEF initially increased up to 4451m and returned to baseline values above 5000m. After descent below 2000m, all values normalized within one day. There were weak negative correlations between AMSS and FEV1, FVC and PEF (r = -0.23, p<0.001). CONCLUSIONS: We found increasing pulmonary restriction at high altitude without a marked reduction of PEF. Assessment of the FEFV-curve at high altitudes with a portable spirometer is a practical method reflecting the true field situation and may provide clinically relevant information (impending pulmonary edema).

Multifocal primary amyloidosis of the airways: Case report and review of the literature.

Primary localized amyloidosis of the airways is an uncommon disorder characterized by amyloid deposits in the airway mucosa. In contrast to systemic amyloidosis other organs are not involved. Among the entities of airway amyloidosis, tracheobronchial amyloidosis is comparatively the most common subtype in the lower respiratory tract and laryngeal amyloidosis in the upper respiratory tract. The pathophysiology of localized airway amyloidosis is poorly understood. The clinical presentation is variable and often non-specific. No general consensus exists with regard to optimal treatment resulting in a variety of modalities used in clinical practice to manage this disorder. We report the case of a 50 year old woman with multifocal localized amyloidosis of the tracheobronchial tree and the upper airways. Tracheobronchial amyloidosis was treated with endoscopic debulking and external beam radiation, sinunasal amyloid deposits were surgically excised and are currently under surveillance. The importance of this extremely rare case lies in the multifocal presentation of an uncommon disorder requiring a multidisciplinary approach to offer optimal treatment including external beam radiation.

Comparison of the effects of moist and dry conditions on dermal repair.

The effects on dermal repair of moist conditions, achieved by covering excised wounds with the adhesive polyurethane dressing OPSITE, and dry conditions, achieved by exposure to air through dry gauze dressings, were compared in full thickness excised wounds on porcine skin during the period from 1 to 21 d after injury. Quantitative studies were made of changes in the populations of neutrophils, macrophages, fibroblasts, and endothelial cells. The number of inflammatory phase cells (neutrophils and macrophages) decreased more rapidly under moist conditions than under dry conditions. There was also a more rapid increase in the number of proliferative phase cells (fibroblasts and endothelial cells) in the moist wounds; by 5 d after injury 66% of the cells of the granulation tissue of the moist wounds were of this type, compared with only 48% of the cells of equivalent areas of the dry wounds. By 21 d after injury the number of fibroblasts in the granulation tissue of the moist wounds had fallen below that in the dry wounds, suggesting that progress from the proliferative into the remodelling phase of repair was more rapid in the moist wounds. It was concluded that there was an acceleration of the inflammatory and proliferative phases of dermal repair in wounds healing under moist conditions when compared with those healing under dry conditions.

Human vertebral cancellous bone surface distribution.

The three-dimensional distribution of bone surface and the bone volume fraction (BV/TV) of 110 human vertebral cancellous bone specimens from seven individuals were measured using a three-dimensional radiographic method (microcomputed tomography). The ratios of the three principal projections of bone surface per total volume were found to be relatively constant for specimens examined in this study. The constancy of the projected surface ratios means that the fraction of the total bone surface oriented in any direction does not change markedly with BV/TV. Bone volume fraction was a good predictor of bone surface per total volume (BS/TV) for a one-parameter nonlinear model (r2 = 0.92). The results of this pilot study suggest that the changes in surface distribution which occur during age-related bone loss are largely predetermined rather than adaptive. The results are also consistent with the idea that cancellous bone tends to maintain a constant ratio of trabecular number for the principal directions. If these inferences from the data are correct, the morphogenetic processes which create the initial adult trabecular pattern become of primary interest. A model was developed which explained the strong relationship between BS/TV and BV/TV. The model was used to demonstrate the importance of morphogenetic processes.

High-dose-rate brachytherapy: dose escalation in three-dimensional miniorgans of the human bronchial wall.

PURPOSE: High-dose-rate (HDR) brachytherapy of human lung cancer is well established, however fractionation schemes and dosages are based mainly on experience. The aim of this investigation was to study the effects of different doses of HDR iridium-192 on normal human bronchial epithelium in three-dimensional miniorgans of the human bronchial wall. METHODS AND MATERIALS: Forty-eight biopsies from normal bronchi were cultivated for 14 days and exposed at random to different doses of HDR iridium 192 (0 Gy, 30 Gy, 45 Gy, 60 Gy, or 75 Gy). Cell viability was assessed immediately after irradiation, after 4 or 18 days by fluorescent staining, and cell damage of the culture was analyzed by light microscopy. Lactate dehydrogenase (LDH) was measured in the supernatant for 4 days. RESULTS: There was no histologically apparent tissue damage regardless of the irradiation dose. The number of nonvital cells increased in irradiated miniorgans depending on the dose used (p < 0. 05 at 75 Gy). This effect occurred early and was less pronounced with time. LDH measurements showed an increase only in the first 24 hours. CONCLUSIONS: Our results confirm that normal bronchial epithelium has a high tolerance to early epithelial damage by irradiation. This model of human bronchial miniorgans is useful for further studies of the effects of irradiation on human bronchi.

Detection of human Ha-ras transcripts in tumor cells by in situ hybridization.

We demonstrate the development of a method for identification of human Ha-ras transcripts in cytological and histological preparations of rodent fibroblasts by RNA-RNA in situ hybridization. Fibroblasts, expressing human Ha- ras at high or a very low level, provide a biological model system to optimize in situ hybridization. For rapid detection we used the radiographic signal from cell smears, in directly overlaid x-ray film. Certain pretreatments of slides are shown to increase nonspecific probe binding. The methods described can be used for rapid detection of oncogene expression in small numbers of cultured cells, without prior extraction and purification of their RNA.

Correlation of mechanical properties of vertebral trabecular bone with equivalent mineral density as measured by computed tomography.

We tried to determine whether mineral-equivalent measurements that were obtained using computed tomography could be used to predict the mechanical properties of vertebral trabecular bone. Vertebral bodies that had been obtained during routine autopsy were evaluated by computed tomography. The mechanical properties of the vertebral trabecular bone were determined by subjecting cylindrical specimens to simple compression until failure occurred. The ultimate strength and elastic modulus were determined from load time curves, using constant displacement rate loading. Atomic absorption spectrophotometry was used to determine the weight per cent calcium of each specimen, and quantitative light microscopy was used to determine area fraction bone. Significant positive correlations were found between the observed mechanical properties of the trabecular bone and the equivalent mineral density as measured by computed tomography. Compressive strength (r = 0.720), elastic modulus (r = 0.574), trabecular calcium density (r = 0.780), and area fraction bone (r = 0.579) were all correlated with the equivalent mineral density.

Human vertebral body apparent and hard tissue stiffness.

Cancellous bone apparent stiffness and strength are dependent upon material properties at the tissue level and trabecular architecture. Microstructurally accurate, large-scale finite element (LS-FE) models were used to predict the experimental apparent stiffness of human vertebral cancellous bone and to estimate the trabecular hard tissue stiffness. Twenty-eight LS-FE models of cylindrical human vertebral cancellous bone specimens (8 mm in diameter, 9.5 mm in height, one each from twenty-eight individuals) were generated directly from microcomputed tomography images and solved by a special purpose iterative finite element program. The experimental apparent stiffness and strength of the specimens were determined by mechanical testing to failure in the infero superior direction. Morphometric measurements including bone volume fraction (BV/TV), three eigenvalues of the fabric tensor and average P(L) were also calculated. The finite element estimate of apparent stiffness explained much of the variance in both experimental apparent stiffness (r2=0.89) and experimental apparent strength (r2=0.87). Stepwise linear regression analysis demonstrated that the LS-FE estimated apparent stiffness was the only significant predictor of experimental apparent stiffness and strength when it was included with all measured morphometric values. Hard tissue stiffness was quite variable between individuals (mean, 5.7 GPa; S.D. 1.6 GPa), but was not significantly related to age, sex, race, weight or morphometric measures for this sample.

Hypertension induced by recombinant human erythropoietin (rHU-EPO) can be prevented by indomethacin. Pathogenetic role of cytosolic calcium.

Hypertension complicating the therapy of renal anemia with rHU-EPO is characterized by an increase in total peripheral vascular resistance, but the mechanisms underlying arteriolar vasoconstriction remain unclear. To assess the role of altered cellular calcium metabolism, resting platelet cytosolic calcium was measured in 12 previously normotensive patients with end-stage renal disease before and after 12 weeks of EPO-therapy, after 12 weeks of combined antihypertensive pharmacotherapy of EPO-induced hypertension, and after 12 weeks of concurrent administration of EPO and indomethacin. Patients with EPO-induced hypertension showed a significant raise in platelet calcium by comparison with calcium levels prior to EPO (179 +/- 15 vs 120 +/- 8 nmol/l), and there was a positive correlation between their blood pressure and platelet calcium levels (r = 0.9, p < 0.001). Antihypertensive therapy of EPO-induced hypertension resulted in a reduction of blood pressure and a reduction of platelet calcium to near normal levels (128 +/- 6 nmol/l). The non-steroidal antiinflammatory drug indomethacin prevented EPO-induced hypertension and EPO-associated alterations in platelet calcium. The results of the present study suggest that EPO-induced hypertension might be related to altered cellular calcium homeostasis. If EPO therapy induces alterations in calcium metabolism not only in platelets but also in vascular smooth muscle cells, these changes in calcium influx may contribute to arteriolar vasoconstriction during EPO therapy.

Detection of K-ras and p53 mutations in bronchoscopically obtained malignant and non-malignant tissue from patients with non-small cell lung cancer.

Molecular screening may increase the likelihood to identify early malignant lesions in non-small cell lung cancer. However the presence of gene mutations in non-malignant bronchial tissue has remained controversial. The present study was carried out to investigate systematically the presence of mutations of the K-ras and p53 gene in bronchial biopsies taken during routine bronchoscopy of normal as well as tumour tissues from a series of 40 patients with histologically verified non-small cell lung cancer (NSCLC). K-ras mutations were analysed with specific detection oligonucleotides, p53 mutations were examined by SSCP analysis. In all biopsies the wildtype of both K-ras and p53 could be detected. The overall frequency of mutations was 14 (35%) with 2 K-ras mutations (5%) and 12 mutations of the p53 gene (30%). In 3 cases (1 ras mutation, 2 p53 mutations) the same mutation could be shown in the tumour biopsy and in the distant normal control. In another case only the normal appearing tissue had a mutation of the p53 gene. All other mutations could be detected in the tumour tissue only. Our data confirm that K-ras mutations and p53 can be detected not only in malignant but also in non-malignant bioptic samples from patients with NSCLC. The use of molecular screening for the early detection of lung cancer may be a promising new approach.

Characterization of subtypes of hypertension in CAPD patients by cyclic guanosine monophosphate.

OBJECTIVE: While most hypertensive patients with end-stage renal disease normalize high blood pressure with fluid removal by continuous ambulatory peritoneal dialysis (CAPD), there is a significant proportion of CAPD patients whose blood pressure can be controlled only by antihypertensive drugs. METHOD AND PATIENTS: To study the hypothesis that such patients are still volume overloaded, we used plasma cyclic guanosine monophosphate (cGMP) as a marker for hydration status. Thirty-two CAPD patients were divided into 3 groups: group 1, normotensive patients (n = 12); group 2, hypertensive patients who normalized their blood pressure with fluid removal (n = 12); group 3, hypertensive patients whose blood pressure was refractory to intensified fluid removal (n = 8). RESULTS: Mean cGMP levels were significantly higher in dialysis-sensitive hypertension (27 +/- 5 pmol/mL) than in dialysis-refractory hypertension (15 +/- 2 pmol/mL), or in normotensive patients (13 +/- 4 pmol/mL). Reduction of excess fluid in volume overloaded hypertensive CAPD patients resulted in a normalization of cGMP levels (14 +/- 8 pmol/mL), but did not affect this volume marker in patients with dialysis-resistant hypertension (10 +/- 4 pmol/mL). CONCLUSION: Plasma cGMP levels are elevated in volume overload-induced hypertension complicating CAPD. Hypertensive CAPD patients whose plasma cGMP levels are within normal limits have raised blood pressure refractory to volume removal. Our findings are consistent with the hypothesis that inadequate removal of excess volume plays a major role in a subset of patients with CAPD hypertension.

Preservation of residual renal function in dialysis patients: effects of dialysis-technique-related factors.

OBJECTIVES: Residual renal function (RRF) is of paramount importance to dialysis adequacy, morbidity, and mortality, particularly for long-term continuous ambulatory peritoneal dialysis (CAPD) patients. Residual renal function seems to be better preserved in patients on CAPD than in hemodialysis (HD) patients. We analyzed RRF in 45 patients with end-stage renal disease (ESRD), commencing either CAPD or HD, to prospectively define the time course of the decline in RRF, and to evaluate dialysis-technique-related factors such as cardiovascular stability and bioincompatibility. STUDY DESIGN: Single-center prospective investigation in parallel design with matched pairs. MATERIALS: Fifteen patients starting CAPD and 15 matched pairs of patients commencing HD were matched according to cause of renal failure and RRF. Hemodialysis patients were assigned to two dialyzer membranes differing markedly in their potential to activate complement and cells (bioincompatibility). Fifteen patients were treated exclusively with the cuprophane membrane (bioincompatible) and the other 15 patients received HD with the high-flux polysulfone membrane (biocompatible). MEASUREMENTS: Residual renal function was determined at initiation of dialytic therapy and after 6, 12, and 24 months. Dry weight (by chest x ray and diameter of the vena cava) was closely recorded throughout the study, and the number of hypotensive episodes counted. RESULTS: Residual renal function declined in both CAPD and HD patients, although this decline was faster in HD patients (2.8 mL/minute after 6 months and 3.7 mL/min after 12 months) than in CAPD patients (0.6 mL/min and 1.4 mL/min after 6 and 12 months respectively). It declined faster in patients with bioincompatible than with biocompatible HD membranes (3.6 mL/min vs 1.9 mL/min after 6 months). Eleven percent of the HD sessions were complicated by clinically relevant blood pressure reductions, but there were no differences between the two dialyzer membrane groups. None of the CAPD patients had documented hypotensive episodes. None of the study patients suffered severe illness or received nephrotoxic antibiotics or radiocontrast media. CONCLUSIONS: The better preservation of RRF in stable CAPD patients corresponded with greater cardiovascular stability compared to HD patients, independently of the membrane used. Furthermore, there was a significantly higher preservation of RRF in HD patients on polysulfone versus cuprophane membranes, indicating an additional effect of biocompatibility, such as less generation of nephrotoxic substances by the membrane. Thus, starting ESRD patients on HD prior to elective CAPD should be avoided for better preservation of RRF.

Bioincompatibility of dialyzer membranes may have a negative impact on outcome of acute renal failure, independent of the dose of dialysis delivered: a retrospective multicenter analysis.

The mortality rate of critically ill patients with acute renal failure (ARF) has remained high. The impact of vigorous intermittent hemodialysis (IHD) on the outcome of ARF has not been validated. In this retrospective multicenter analysis, 154 patients with ARF were treated daily (intensive) or on alternate days (conventional) using complement and cell activating cuprophane (bioincompatible) or high-flux polysulfone dialyzer membranes with insignificant effects on circulating complement or cells (biocompatible). At initiation of IHD, all four groups were similar in patient characteristics and ARF factors. The use of synthetic membranes resulted in a reduced mortality rate (18% vs 45%; p < 0.001) and shorter duration of ARF (8 vs 15 sessions; p < 0.001). Daily IHD with cellulose based membranes tended to increase mortality rates compared with conventional cuprophane dialysis (37% vs 53%). Intensive IHD with polysulfone membranes resulted in a further decrease in overall mortality rates (15% vs 22%). This retrospective analysis shows that bioincompatibility of dialyzer membranes may be more important for the outcome of patients with ARF than the dose of dialysis. Its impact on outcome occurs independently of the dose of dialysis delivered.

The evaluation of a haemoperfusion device in conscious dogs.

A newly designed charcoal haemoperfusion device was evaluated by repeated haemoperfusion of conscious dogs. The procedure was tolerated well and the incidence of side effects was low. Alterations to haematology were small with platelet drops of only 9% and only minor disturbances to plasma chemistry were seen.

Dissociation between high anti-PR3 titers (c-ANCA) and the clinical course of disease in a case of Wegener granulomatosis.

In May 1984 a 58-year-old woman presented with a broad spectrum of clinical symptoms including malaise, arthralgia, hemoptysis and dyspnea, proteinuria and hematuria and a vasculitic necrotizing rash. Bronchial biopsies revealed subglottic granulomatous lesions and renal biopsies showed necrosis, extracapillary proliferation and crest formation, confirming the diagnosis of Wegener granulomatosis. Positive c-ANCA and anti-proteinase 3 subfraction (anti-PR3) titers were first analysed in 1991. Clinical remission was achieved by standard immunosuppressive therapy and renal function was stabilised. Several minor relapses were treated with pulsed intravenous cyclophosphamide but the symptoms could not be completely controlled. Eight years after the onset of disease, a dramatic increase in anti-PR3 titers was observed (34438 U/ml, normal range < 10, ELISA), followed 3 months later by a clinically apparent relapse. Immunosuppressive therapy was reinstituted without clinical improvement. At this point plasmapheresis resulted in an amelioration of clinical symptoms as well as a reduction in anti-PR3 titers. Concomitant immunosuppressive therapy was administered with oral corticosteroids. Forty days later anti-PR3 titers increased, reaching 75000 U/ml twelve months later, however this time without associated clinical symptoms. During the following months the patient had a further transient deterioration of pulmonary and renal function due to secondary bacterial infection which was successfully treated with antibiotics. A nephritic sediment was not present during these episodes. Curiously, the anti-PR3 titers have remained excessively elevated for the last three years.