Pulmonary involvement by Niemann-Pick disease. A report of six cases.

AIMS: Although pulmonary involvement is a known cause of morbidity in Niemann-Pick disease, histological features in the lung are not well characterized. The purpose of this study is to document the histological features seen in pulmonary involvement by types B and C Niemann-Pick disease and to correlate them with clinical and imaging data. METHODS AND RESULTS: Surgical lung biopsies from six patients (four with type B and two with type C disease) were reviewed and all showed diffuse endogenous lipid pneumonia, with lesser involvement of the interstitium by fibrosis and foamy macrophage accumulation. In type B disease only, there was also fine cytoplasmic vacuolation within the cytoplasm of ciliated epithelial cells. Neither disease showed foamy changes within pneumocytes. One patient had a bronchial cast removed on whole lung lavage. Electron microscopy showed abnormal lamellar inclusions within lysosomes of affected cells in type B disease. In patients with type C disease, biopsies were undertaken as part of investigations into acute respiratory failure in the context of multiorgan systemic presentation. Three patients with type B disease had clinical disease limited to the lung, all adults (mean age of 40 years) with unexplained diffuse parenchymal lung disease and mainly ground-glass shadowing on high-resolution computed tomography. CONCLUSIONS: Niemann-Pick disease should be considered for any patient with unexplained diffuse endogenous lipid pneumonia, even when disease is limited to the lungs and presentation is during adulthood.

Extracellular thioredoxin levels are increased in patients with acute lung injury.

BACKGROUND: Acute lung injury (ALI) and its extreme manifestation the acute respiratory distress syndrome (ARDS) complicate a wide variety of serious medical and surgical conditions. Thioredoxin is a small ubiquitous thiol protein with redox/inflammation modulatory properties relevant to the pathogenesis of ALI. We therefore investigated whether thioredoxin is raised extracellulary in patients with ALI and whether the extent of any increase is dependent upon the nature of the precipitating insult. METHODS: Bronchoalveolar lavage (BAL) fluid and plasma samples were collected from patients with ALI (n=30) and healthy controls (n=18, plasma; n=14, BAL fluid). Lung tissue was harvested from a separate group of patients and controls (n=10). Thioredoxin was measured by ELISA in fluids and by immunohistochemistry in tissue. Interleukin (IL)-8 levels were determined by ELISA. Disease severity was assessed as APACHE II and SOFA scores. RESULTS: BAL fluid levels of thioredoxin were higher in patients with ALI than in controls (median 61.6 ng/ml (IQR 34.9-132.9) v 16.0 ng/ml (IQR 8.9-25.1), p<0.0001); plasma levels were also significantly higher. When compared with controls, sections of wax embedded lung tissue from patients with ALI showed greater positive staining for thioredoxin in alveolar macrophages and type II epithelial cells. BAL fluid levels of thioredoxin correlated with IL-8 levels in BAL fluid but not with severity of illness scores or mortality. BAL fluid levels of thioredoxin, IL-8, and neutrophils were significantly greater in patients with ALI of pulmonary origin. CONCLUSIONS: Extracellular thioredoxin levels are raised in patients with ALI, particularly of pulmonary origin, and have a significant positive association with IL-8. Extracellular thioredoxin levels could provide a useful indication of inflammation in ALI.

Cystic fibrohistiocytic tumours presenting in the lung: primary or metastatic disease?

AIMS: Cystic fibrohistiocytic tumour of the lung is a rare proliferative process. Its histogenesis is uncertain, but evidence suggests that some cases represent metastatic disease from apparently indolent skin lesions, namely cellular fibrous histiocytomas. This study presents four cases and reviews the literature concerning this pattern of disease and its aetiology. METHODS AND RESULTS: All patients were male (age range 35-54 years). Two presented with recurrent haemoptysis. Two cases had histories of cutaneous fibrohistiocytic lesions in the chest wall, excised 10 and 23 years prior to presentation with lung disease. Imaging data showed multiple bilateral cystic lung lesions in all four patients with nodular cavitating opacities seen on high-resolution computed tomography scans. Microscopy showed variably dilated thin-walled cystic airspaces lined by cuboidal epithelium and an underlying layer of mildly pleomorphic spindle cells with slightly wavy morphology and storiform architecture, admixed with inflammatory cells. Tumour cells stained for CD68 in three of four cases. All cases were negative for CD34. All patients were alive with disease, although one required pneumonectomy for intractable haemoptysis. CONCLUSION: This study and a review of published cases show that the majority of cystic fibrohistiocytic tumours of the lung probably represent metastases from cellular fibrous histiocytomas. However, rare cases may be either primary in origin or the primary site remains occult; the term cystic fibrohistiocytic tumour remains appropriate for such cases.

Giant lamellar bodies as a feature of pulmonary low-grade MALT lymphomas.

AIMS: Giant lamellar bodies (GLBs) are rare pulmonary inclusions, most frequently described in sclerosing haemangiomas. Following a recent report of their presence in a case of pulmonary lymphoma of MALT origin, our aims were to determine their frequency in pulmonary lymphoproliferative disorders, examine their structure and investigate their aetiology further. METHODS AND RESULTS: We reviewed a series of 29 pulmonary lymphomas (23 low-grade, six high-grade) and 18 cases of reactive pulmonary lymphoid hyperplasia. Five of 23 (22%) low-grade lymphomas contained GLBs, 4/4 of which stained for surfactant apoprotein A but not for surfactant apoprotein B. No GLBs were seen in 18 cases of reactive pulmonary lymphoid hyperplasia or six high-grade primary pulmonary lymphomas. Ultrastructural examination revealed concentrically arranged extracellular material forming roughly spherical structures up to 25 microm in diameter. The GLBs were often surrounded by foamy cells and cholesterol clefts, supporting an origin, at least in part, from products of cell breakdown and surfactant degradation. CONCLUSION: These findings support the idea that the presence of lamellar bodies is in part due to stasis of products arising from degradation of surfactant, in association with certain types of chronic pulmonary pathology. Given their absence in reactive pulmonary lymphoid hyperplasia, the presence of GLBs as an epiphenomenon in a pulmonary lymphoid infiltrate should warrant careful investigation with regard to the diagnosis of low-grade MALT lymphoma.

[Smoking among academics, non-academics and students of the Universidad de Concepción]. / Tabaquismo en académicos, no académicos y estudiantes de la Universidad de Concepción.

BACKGROUND: Effective smoking cessation campaigns require as baseline, precise estimations of smoking habits in different populations. AIM: To assess the prevalence of smoking in academic, non-academics workers and student of the University of Concepción. MATERIAL AND METHODS: In a random and stratified sample of 272 workers (including academics) and 1146 students, a previously validated, self administered questionnaire about smoking was applied. Daily smoking was defined as smoking seven or more cigarettes per week and occasional smoking as smoking less than seven cigarettes per week. RESULTS: The prevalence of smoking was 23% among academics, 34% among non-academic workers and 44% among students. Nineteen percent of men and 16% of women were occasional smokers; 23% of men and 25% of women were daily smokers. Students started smoking at 15 +/- 2 years old and workers did so at 18 +/- 3 years old. The greater influence about smoking came from parents. Workers from the administrative services and from the natural sciences faculty had the higher prevalence of the habit. The total annual cost of smoking was $33,000,000 (US$62,000). CONCLUSIONS: The prevalence of smoking at the University of Concepción is higher among students than workers. Quitting programs are urgently needed.

Malignant myxoid endobronchial tumour: a report of two cases with a unique histological pattern.

AIMS: To present two cases of malignant endobronchial myxoid tumours with a highly distinctive sarcomatoid pattern not previously described at this site, and discuss their histogenesis in relation to previously documented endobronchial neoplasms. METHODS AND RESULTS: Both tumours presented in young adult females and were purely sarcomatoid with interweaving cords of small uniform, rounded or slightly elongated cells lying within a myxoid stroma. The stroma was alcian blue positive, but sensitive to hyaluronidase in both cases. The tumour cells contained a small volume of periodic acid-Schiff-positive eosinophilic cytoplasm and stained positively for vimentin only, but there also was a prominent background population of CD68-positive dendritic cells. Ultrastructural studies showed that the tumour cells contained an excess of rough endoplasmic reticulum, with some of the cisternae appearing dilated, and scalloping of the cell surfaces, although no intracisternal tubules were identified. CONCLUSIONS: Although the histological pattern was most reminiscent of extraskeletal myxoid chondrosarcoma, the sensitivity of the stroma to pretreatment with hyaluronidase precluded the diagnosis. However, there were similarities with the sarcomatoid component of malignant salivary gland-type mixed tumours of the lung and this tumour possibly represents a variant of a bronchial gland tumour. Despite this uncertainty over origin, this pattern should be recognized as part of the differential diagnosis of myxoid tumours in the lung, as an apparently indolent type of malignant endobronchial neoplasm.

Investigation and diagnosis of diarrhea caused by sodium phosphate.

Because there are no published reference values for fecal phosphate concentration or output, diagnosing surreptitious use of phosphate laxatives has been difficult. The purposes of this study were to determine normal fecal phosphate levels and to quantitate and chemically analyze diarrhea produced by sodium phosphate. Timed stool collections were obtained from 20 normal subjects during 25 study periods (normal controls), from 27 normal subjects with diarrhea induced by a variety of laxatives not containing phosphate during 234 study periods (diarrhea controls), and from 10 normal subjects during 14 periods after ingestion of 45 or 22.5 ml of a commercially available 66% sodium phosphate solution (Fleet Phospho-Soda). All stools were analyzed for soluble phosphate concentration, and daily output was calculated. The upper limits of normal for soluble fecal phosphate concentration and output, derived from the normal controls and diarrhea controls, respectively, were 33 mmol/liter and 15 mmol/day. Diarrhea produced by 45 ml of sodium phosphate was watery and voluminous, with fecal weights averaging 1078 g/day (range 601-1713 g/day). Measured fecal phosphate concentrations and outputs averaged 85 mmol/liter and 92 mmol/day, respectively, and all values were significantly elevated. Soft, less voluminous stools were produced with 22.5 ml of sodium phosphate but all had an abnormally high soluble phosphate concentration and 24-hr output. In conclusion, the upper limits of normal for soluble fecal phosphate concentration and output established in this study should be useful in the chemical diagnosis of phosphate-induced diarrhea.

Echocardiography and pathology of left ventricular "false tendons".

The anatomic incidence of left ventricular false tendons has been determined in 100 hearts obtained from consecutive autopsies on patients who had a wide variety of cardiac conditions. In this series, an anomalous band was found in 34 cases. A retrospective two-dimensional (2D) echocardiographic study was able to identify false tendons in only 18 percent of cases with anatomic evidence of them, indicating 2 mm as the limit of resolution of 2D echocardiography even with appropriate projections. Finally, the histologic examination has shown false tendons to contain conduction tissue and thus it is assumed to be intracavitary radiations of the bundle of His. This last consideration introduces new physical and electrophysiologic implications.

Heterologous antigenicity induced in human aortic homografts during preservation.

A series of rabbit experiments has been carried out to investigate the potential antigenicity of the heat-treated foetal calf serum which is commonly used to enhance viability of preserved aortic homograft valves. In all presensitised animals, the calf serum content of the nutrient medium which infiltrated the aortic wall during preservation provoked a heavy second-set reaction. It is concluded that heat-treated foetal calf serum is a potent heterologous antigen and should not be used for preserving human tissue selected for transplantation.

Damage of porcine aortic valve tissue caused by the surfactant sodiumdodecylsulphate.

The Hancock T6 treatment uses 1% sodiumdodecylsulphate (SDS) to prevent or delay calcification in porcine aortic or pericardial bioprostheses. In the current study fresh and glutaraldehyde fixed porcine aortic cusps were treated in 1% SDS. The hydrothermal stability, the histological and the electronmicroscopic appearance of the tissue were assessed and compared before and after treatment. The results suggest that the 1% SDS solution destroys the fresh material causing acellularity, extreme fragmentation and swelling of the collagen, together with a significant loss of hydrothermal stability. Glutaraldehyde fixation prior to SDS treatment seems to provide protection against the harmful effects of the 1% SDS, with only one exception on electronmicroscopic examination where foci of collagen degeneration were found.

Left ventricular mass, volume and biopsy analysis in prediction of ventricular function after surgery for chronic aortic regurgitation.

The serial application of electrocardiography and echocardiography to 67 selected patients undergoing valve replacement for chronic severe aortic regurgitation, documented regression of hypertrophy and chamber size within six to twelve months of surgery in all cases experiencing haemodynamic improvement. Those patients who had persistently increased patterns of myocardial hypertrophy and abnormal end-diastolic dimensions in the presence of normal prosthetic (homograft) function usually had persistent, irreversibly depressed myocardial function postoperatively. Preoperative noninvasive and angiographic characteristics could not predict ventricular function after surgery. Thus we could not precisely define what level of depressed ventricular performance or what degree of dilatation and myocardial hypertrophy constituted an irreversible state from this data. Although operative factors such as myocardial protection during cardiopulmonary bypass may influence postoperative cardiac performance, preoperative histological and histochemical data was useful in delineating irreversible morphological and function changes contributing to a depressed cardiac function, and therefore may be of prognostic importance.

Comparison of the haematoxylin basic fuchsin picric acid method and the fluorescence of haematoxylin and eosin stained sections for the identification of early myocardial infarction.

A retrospective study has been carried out on the necropsy material from 30 patients who have died after a clinically diagnosed myocardial infarction. This study has been undertaken to compare the reliability of the fluorescence of infarcted myocardium when stained by haematoxylin and eosin and an adjacent section stained by the haematoxylin basic fuchsin picric acid (HBFP) method to detect early ischaemia. The results showed that the fluorescence technique is reliable, reproducible and coincides with the findings obtained by HBFP stain.

Irreversible morphological changes contributing to depressed cardiac function after surgery for chronic aortic regurgitation.

The timing of surgery in chronic aortic regurgitation remains a difficult problem. To identify variables predictive of postoperative haemodynamic improvement, changes in left ventricular mass, volume, morphology, and histochemistry were analysed in 67 patients undergoing surgery for chronic aortic regurgitation. Patients were divided into two groups: those in whom the left ventricular echo diameters returned to normal after operation (51 patients, group A), and those with postoperative dilatation (16 patients, group B). A preoperative biopsy was obtained in all patients; postoperative tissue samples were available in 13 patients (five from group A, eight from group B). Data were correlated with the postoperative clinical, haemodynamic state over a follow-up period of three years. Regression of hypertrophy was usually incomplete. Echocardiographic and angiographic data could not define the type and degree of dysfunction which was irreversible. Massive fibre hypertrophy (mean 34.1 micrometers), moderately or severely increased interstitial fibrous tissue, reduced levels of the myofibrillar and mitochondrial enzymes adenosine triphosphates and succinate dehydrogenase in pre- and post-operative tissue samples correlated with persistent dilation, cardiac failure, and early death (group B). Irreversible morphological and functional changes contributed to a depressed cardiac function after operation. Preoperative ventricular biopsies are thus of prognostic importance in volume overload.

Electron microscopic investigation of endomyocardial biopsy samples in hypertrophy and cardiomyopathy. A semiquantitative study in 48 patients.

Electron microscopic and statistical analyses of 66 right ventricular biopsies from 48 patients were undertaken to investigate whether quantitative differences exist between those patients with "ordinary" myocardial hypertrophy and those suffering from a form of cardiomyopathy. The electron microscopic changes were scored and correlated with hemodynamic variables such as ejection fraction (EF), left ventricular end-diastolic pressure (LVEDP) and length of history. The patients were followed for an average of 22.5 months, permitting an assessment of prognosis. The results show that the three diagnostic groups--"ordinary" hypertrophy, hypertrophic cardiomyopathy (HOCM) and congestive cardiomyopathy (COCM)--overlap, but crossover of sarcomeres is more frequent in patients in whom HOCM is diagnosed. Except for a tenuous relationship between EF, and the electron microscopy (EM) (r = -0.46, p less than 0.1) and between LVEDP and EM score (r = 0.61, p less than 0.01), in the COCM group, no correlation could be established between EF, LVEDP and length of history when the patients were grouped according to histologic or clinical diagnosis. This study shows that the various claims regarding relationships between morphologic changes and the functional status of patients or prognosis cannot be confirmed.

The effect of 5-fluorocytosine on the germination of Aspergillus fumigatus and on subsequent nuclear division.

5-Fluorocytosine (5FC) inhibits the germination of the conidia of A. fumigatus. This is different from the lack of effect of 5FC on hyphal formation from blastospores of C. albicans because, unlike C. albicans, A. fumigatus requires DNA synthesis for germination, and this is inhibited by 5FC. A modified fluorescent Feulgen method has been developed to stain fungal nuclei in the presence and absence of 5FC. This method has shown that hyphae treated with 5FC have fewer nuclei than untreated hyphae. During hyphal growth, DNA synthesis and hyphal elongation in A. fumigatus are equally inhibited by 5FC. This is different from the differential effect of 5FC on C. albicans when hyphal elongation continues during an inhibition of DNA synthesis. The equal inhibition in A. fumigatus is clearly not unbalanced growth and so the action of 5FC on A. fumigatus is merely fungistatic.

Critical analysis of endomyocardial biopsies from patients suspected of having cardiomyopathy. II: Comparison of histology and clinical/haemodynamic information.

Endomyocardial biopsies showing histological evidence of "ordinary" hypertrophy or changes compatible with congestive cardiomyopathy (COCM) were obtained from 125 patients. Statistical analysis compared histological/morphometric data with clinical/haemodynamic findings such as ejection fraction, left ventricular end-diastolic pressure, and length of history. Patients were grouped either according to the histological description or the clinical diagnosis. Comparison of the morphological description with the final clinical diagnosis was also undertaken. Follow-up of the patients was between two and 66 months. The results of the statistical analyses showed no correlation between quantitative, morphological assessment and either clinical information, that is length of history and subsequent course, or the haemodynamic variables. In 86 per cent of cases a rough agreement between the morphological description and the clinical diagnosis was obtained, but no specific pattern permitting a morphological diagnosis of COCM was established. The findings suggest that pronounced topographic variation in biopsy material exists and that, therefore, the severity of COCM or its prognosis cannot be assessed from histological changes.

Carpal tunnel release under local anesthesia: evaluation of the outpatient procedure.

In 100 consecutive cases of carpal tunnel release done under local anesthesia in an outpatient ambulatory care operating room, 93 had satisfactory results at 6 months without any complications. Two patients developed a neuroma of the palmar cutaneous branch of the median nerve, and five showed early signs of reflex sympathetic dystrophy. These complications are discussed, as well as the prevention of other complications of this procedure.