Lung histopathological findings in fatal pandemic influenza A (H1N1) / Resultados histopatológicos pulmonares en la gripe a (H1N1) pandémica letal

Objective: To describe the lung pathological changes in influenza A (H1N1) viral pneumonia. We studied morphological changes, nitro-oxidative stress and the presence of viral proteins in lung tissue. Methods and patients: Light microscopy was used to examine lung tissue from 6 fatal cases of pandemic influenza A (H1N1) viral pneumonia. Fluorescence for oxidized dihydroethydium, nitrotyrosine, inducible NO synthase (NOS2) and human influenza A nucleoprotein (NP)(for analysis under confocal microscopy) was also studied in lung tissue specimens. Results: Age ranged from 15 to 50 years. Three patients were women, and 5 had preexisting medical conditions. Diffuse alveolar damage (DAD) was present in 5 cases (as evidenced by hyaline membrane formation, alveolo-capillary wall thickening and PMN infiltrates), and interstitial fibrosis in one case. In the fluorescence studies there were signs of oxygen radical generation, increased NOS2 protein and protein nitration in lung tissue samples, regardless of the duration of ICU admission. Viral NP was found in lung tissue samples from three patients. Type I pneumocytes and macrophages harbored viral NP, as evidenced by confocal immunofluorescence microscopy. Conclusions: Lung tissue from patients with pandemic influenza A (H1N1) viral pneumonia shows histological findings consistent with DAD. Prolonged nitro-oxidative stress is present despite antiviral treatment. Viral proteins may remain in lung tissue for prolonged periods of time, lodged in macrophages and type I pneumocytes (AU)

Objetivo: Describir la histopatología pulmonar de pacientes que fallecieron con neumonía por virus de la influenza A (H1N1), el tipo celular infectado por el virus y la presencia de stress oxidativo y nitrosativo. Métodos: Hemos examinado tejido pulmonar de 6 pacientes fallecidos en la UCI con el diagnóstico de infección por el virus influenza A (H1N1) (15-50 años de edad) mediante (i) microscopía óptica, (ii) microscopia confocal con tinciones específicas para diferentes tipos celulares (aquoporina 5, factor Von Willebr and, proteína D del surfactante), (iii) inmunofluorescencia (IF) parasonda de dihidroetidio oxidado, óxido nítrico sin tasa inducible (NOS2), anti-3-nitrotirosina y nucleoproteína (NP) del virus de la influenza A (H1N1).Resultados: (1) En 5 casos se encontró daño alveolar difuso (DAD), evidenciado mediante la observación de membranas hialinas, engrosamiento de la pared alveolo-capilar e infiltración de PMN, asociado con hemorragia intensa en un paciente. Un caso presentó fibrosis intersticial.(2) Se demostró en todos los casos aumento de la inmuno-reactividad para DHE oxidado, NOS2y 3-nitrotirosina independientemente de la duración de la estancia en la UCI. (3) Se encontró NP viral en tres pacientes. (4) El virus se localiza en los neumocitos tipo I y en macrófago salveolares. Conclusiones: El tejido pulmonar de pacientes fallecidos con neumonía por virus de la influenza A (H1N1) evidencia hallazgos histológicos compatibles con DAD. El estrés nitro-oxidativo prolongado está presente a pesar del tratamiento antiviral. Las proteínas virales pueden permanecer en el tejido pulmonar durante períodos prolongados de tiempo, albergándose en los macrófagos y neumocitos tipo I (AU)

Lung histopathological findings in fatal pandemic influenza A (H1N1).

OBJECTIVE: To describe the lung pathological changes in influenza A (H1N1) viral pneumonia. We studied morphological changes, nitro-oxidative stress and the presence of viral proteins in lung tissue. METHODS AND PATIENTS: Light microscopy was used to examine lung tissue from 6 fatal cases of pandemic influenza A (H1N1) viral pneumonia. Fluorescence for oxidized dihydroethydium, nitrotyrosine, inducible NO synthase (NOS2) and human influenza A nucleoprotein (NP) (for analysis under confocal microscopy) was also studied in lung tissue specimens. RESULTS: Age ranged from 15 to 50 years. Three patients were women, and 5 had preexisting medical conditions. Diffuse alveolar damage (DAD) was present in 5 cases (as evidenced by hyaline membrane formation, alveolo-capillary wall thickening and PMN infiltrates), and interstitial fibrosis in one case. In the fluorescence studies there were signs of oxygen radical generation, increased NOS2 protein and protein nitration in lung tissue samples, regardless of the duration of ICU admission. Viral NP was found in lung tissue samples from three patients. Type I pneumocytes and macrophages harbored viral NP, as evidenced by confocal immunofluorescence microscopy. CONCLUSIONS: Lung tissue from patients with pandemic influenza A (H1N1) viral pneumonia shows histological findings consistent with DAD. Prolonged nitro-oxidative stress is present despite antiviral treatment. Viral proteins may remain in lung tissue for prolonged periods of time, lodged in macrophages and type I pneumocytes.

Fine-needle aspiration biopsy of liver masses: diagnostic value and reproducibility of cytological criteria.

There are many helpful cytological criteria for the diagnosis of liver fine-needle aspiration biopsies (FNABs), but none of them are pathognomonic of primary or metastatic tumors. We analyzed the diagnostic value and reproducibility of 28 cytological parameters in FNABs from 140 hepatic masses, including 29 benign lesions, 49 hepatocellular carcinomas (HCCs), and 62 metastatic tumors, encompassing 48 adenocarcinomas (ACAs). Five different observers evaluated each sample, and the interobserver and intraobserver agreement was studied. Multivariable analysis showed that the criteria more closely associated with malignancy were irregular nuclear contour, three-dimensional cell groups, and atypical naked nuclei. Capillaries separating tumor cells and granular cytoplasm were strongly associated with HCCs, while eccentrically placed nuclei and necrosis were most commonly seen in ACAs and in metastatic tumors. The intraobserver and interobserver agreement was excellent for the final cytological diagnosis, and there was fair to very good interobserver agreement for 22 of the 28 criteria studied. Architectural features were less reproducible than pure cytological criteria. Intraobserver variability was not influenced by the years of experience in the field. A precise and strict definition of terminology rendered a better reproducibility of the cytological criteria.

Hemodynamic, biochemical and morphological changes induced by aminoguanidine in normal and septic sheep.

OBJECTIVE: To define the acute hemodynamic, metabolic, and morphological changes induced by aminoguanidine, a selective iNOS inhibitor, in septic sheep. DESIGN: Prospective, nonrandomized animal study. SETTING: Animal research facility in a University Hospital. INTERVENTIONS: Adult sheep, sedated and mechanically ventilated, were monitored with a pulmonary arterial catheter and an ultrasonic blood flow probe in the mesenteric artery, to measure the systemic (Q(TOT)I) and the mesenteric (Q(MES)I) blood flow indices, and an ileal tonometer. Four groups of sheep were studied: nonseptic, septic, nonseptic treated with aminoguanidine, and septic treated with aminoguanidine (100 mg kg(-1) h(-1)) (n = 6 for each group). Sepsis was induced by the intravenous administration of E. coli. Hemodynamic and biochemical parameters were measured during 300 min. Histological changes in the liver and small intestinal mucosa were analyzed at the end of the experiment. MEASUREMENTS AND MAIN RESULTS: In nonseptic animals, aminoguanidine slightly increased mean systemic arterial pressure (MAP), decreased Q(TOT)I, and increased vascular resistance index (SVRI) and pulmonary vascular resistance index. Q(MEs)I did not change and Q(MES)I/Q(ToT)I increased. Aminoguanidine also induced intestinal intramucosal hypercarbia, hyperlactatemia, acidemia, hypoglycemia, and morphological signs indicative of tissue ischemia in the small intestinal mucosa. In septic sheep, aminoguanidine increased SVRI and MAP only at 4 h after the septic challenge and thereafter, and worsened gas exchange. CONCLUSIONS: In this model, exogenous administration of aminoguanidine induces beneficial hemodynamic effects 4 h after the septic challenge. In normal animals, however, aminoguanidine was associated with hypoglycemia, acidosis, hyperlactatemia, and intestinal mucosal ischemia.

Modulation of systemic hemodynamics by exogenous L-arginine in normal and bacteremic sheep.

OBJECTIVE: To investigate whether exogenous L-arginine, the substrate for nitric oxide synthase, modulates systemic hemodynamics in sepsis. DESIGN: Prospective, controlled study in a sheep model of sepsis. SETTING: Animal research facility in a university hospital. SUBJECTS: Adult sheep weighing between 35 and 55 kg. INTERVENTIONS: Adult sheep sedated and mechanically ventilated, were monitored with a pulmonary arterial catheter and an ileal tonometer. Four groups of sheep were studied: nonseptic, septic, nonseptic treated with L-arginine, and septic treated with L-arginine. Sepsis was induced by the intravenous administration of Escherichia coli (1.5x10(8) colony-forming units/kg for 30 mins). L-arginine was administered as an intravenous bolus (200 mg/kg for 10 mins) before the septic challenge followed by 200 mg/kg/hr for 300 mins. MEASUREMENTS AND MAIN RESULTS: Sepsis induced a state of acidosis, hyperlactatemia, hypoxemia, and gastric intramucosal acidosis. During the first 30 mins after the septic challenge, there was a decrease in cardiac index and blood pressure, and an increase in systemic vascular resistance. Thereafter, blood pressure returned to baseline values, and systemic vascular resistance fell. Treatment with L-arginine in nonseptic sheep did not induce any biochemical or hemodynamic effect. In septic sheep, treatment with L-arginine was associated with a greater increase in systemic vascular resistance during the first 30 mins, and a more marked decrease in blood pressure and systemic vascular resistance after 180 mins. CONCLUSIONS: Exogenous administration of L-arginine does not induce hemodynamic effects in normal animals, exacerbates the acute vasoconstriction associated with the intravenous infusion of E. coli and potentiates the sepsis-induced vasodilation. Our results suggest that a) nitric oxide production is not constitutively modulated by exogenous L-arginine, b) L-arginine probably enhances the sepsis-induced sympathetic discharge, and c) L-arginine becomes rate-limiting for the formation of nitric oxide at approximately 3 hrs after the initiation of the septic challenge.

[Some details on the updating of an animal vesical tumor model]. / Algunos detalles en la puesta a punto de un modelo animal de tumor vesical.

OBJECTIVES: To describe the problems found by the authors with a murine vesical tumour model. METHODOLOGY: Review of the primary aspects of the choice of animal and challenge of murine vesical tumours. Also, analysis of the relationship between bladder size, estimated by palpation, and volume obtained after death of animals and measurement of bladder dimensions. Finally, establishment of specificity and positive predictive value (PPV) of the abdominal examination in bladders with size > or = 4 mm. RESULTS: Vesical tumours challenging in small-sized experimental animals is simple and requires minimum logistics. With regard to estimate of vesical dimensions, the r coefficient between the methods used by the authors to assess vesical volume reached 0.97 (r2 = 0.95). Specificity and PPV of abdominal digital examination in bladders > or = 4 mm reached 100%. CONCLUSIONS: Handling of C57BL/6 mice requires very short training periods. Abdominal digital examination allows to extrapolate size of the bladder and to select tumour-bearing animals when the estimated vesical size is equal to or greater than 4 mm.

Autopsy as quality assurance in the intensive care unit.

A prospective study of 100 autopsies was carried out. The clinical and pathologic diagnoses were made independently by intensivists and pathologists; at the end of the study, the differences were determined. There were seven Class I errors (which if detected before death, would probably have led to a change in management that might have resulted in cure or prolonged survival), six of these relating to the basic disease and one to the cause of death. Class II errors occurred in 15 patients, ten relating to the basic disease and five to the cause of death. In 61% of the patients, the major and minor diagnoses coincided. In 77% of the patients, the major diagnoses coincided. No relationship was found between the incidence of Class I and Class II errors and the length of the patients' stay in the ICU.

Radiographic findings for the adult respiratory distress syndrome in patients with peritonitis.

Ninety-seven consecutive patients admitted to the ICU with peritonitis were studied. Of these, 66 (68%) died and autopsies were performed on 38 (58%). Twelve of the 38 autopsied patients showed pathologic criteria of adult respiratory distress syndrome (ARDS); 26 did not. Chest x-rays of the 38 autopsied patients were examined and 9 (75%) of the 12 patients with histologic criteria of ARDS, specifically, moderate or severe fibrosis, had decreased pulmonary longitudinal diameter on serial chest x-rays. The remaining 3 (25%) patients did not have this specific finding. Of the 26 patients without pathologic criteria of ARDS, only 2 (8%) had reduction in pulmonary longitudinal diameter. We conclude that a marked reduction in the pulmonary longitudinal diameter is highly suggestive of ARDS and especially useful in differentiating ARDS from bilateral pneumonia.

Pulmonary vascular lesions in the toxic oil syndrome in Spain.

A histological study was made of pulmonary arteries at the necropsies of nine patients who died after the ingestion of denatured rapeseed oil during the epidemic which occurred in Spain in May 1981. Lesions found in the elastic pulmonary arteries were characterised by pronounced intimal proliferation of an oedematous nature, accumulation of large vacuolated cells within the media, and loss of vascular smooth muscle. In muscular pulmonary arteries there was pronounced medial hypertrophy and intimal proliferation, which was so severe in one case that it completely occluded the arterial lumen. Foamy cells were found in the intima. Muscularisation was seen in the walls of pulmonary arterioles.

ARDS due to ingestion of denatured rapeseed oil.

Among the different etiologies of noncardiogenic acute pulmonary edema is found the administration or ingestion of various substances. We have studied two patients with ARDS secondary to the ingestion of toxic oil. Both patients presented similar roentgenographic findings characterized by interstitial and alveolar infiltration in "butterfly" distribution, pleural effusion, and a normal cardiac silhouette. The two cases also showed a pulmonary compliance either normal or slightly diminished. With the aid of artificial ventilation, they evolved favorably, gaseous exchange and chest x-ray films returning to normal 16 and 22 days after admission.

Endocarditis caused by B fragilis.

A 54-year-old man had had an acute anterior myocardial infarction nine years prior to this hospital admission. Since that time he had been asymptomatic with the exception of occasional episodes of precordial chest pain. The patient died from septic shock on the tenth day after the present admission. On autopsy there was an old myocardial infarct with aneurysmal dilatation of the left ventricle which contained a large thrombus with multiple abscesses. Septic infarcts were also found in the left kidney and the left temporal lobe of the brain.

[Giant cells in the glomerulus and renal amyloid. Report of a case (author's transl)]. / Células gigantes glomerulares y amiloidosis renal. Aportación de un caso nuevo y revisión de la literatura.

A case of primary amyloidosis in which multinucleated giant cells occurred in relation to amyloid deposits in the renal-glomerulus and in multiple other organs is reported. The ubiquity of multinucleated giant cells distinguishes the present case from those previously described in the literature. It is felt that the finding of multinucleated giant cells next to amyloid deposits in the walls of blood vessels and interstitium of several organs adds support to the theory that these cells function as macrophages. It is also suggested that in cases of amyloidosis with severe renal involvement, emergence of giant cells might be promoted by chronic dialysis.