Imaging in neonatal respiratory disease.

The purpose of this review is to describe the current state of the art in clinical imaging for NICU patients, divided into major areas that correspond to likely phenotypes of neonatal respiratory disease: airway abnormalities, parenchymal disease, and pulmonary vascular disease. All common imaging modalities (ultrasound, X-ray, CT, and MRI) are discussed, with an emphasis on modalities that are most relevant to the individual underlying aspects of disease. Some promising aspects of dynamic and functional imaging are included, where there may be future clinical applicability.

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.

Elastin expression in very severe human COPD.

Alveolar elastic fibres are key targets of proteases during the pathogenesis of chronic obstructive pulmonary disease (COPD). In the current study, we hypothesised that a response to injury leads to enhanced alveolar elastin gene expression in very severe COPD. Lung samples obtained from 43 patients, including 11 with very severe COPD (stage 4), 10 donors, 10 with moderate/severe COPD (stage 2-3) and 12 non-COPD subjects, were analysed for elastin mRNA expression by real-time RT-PCR and in situ hybridisation. Alveolar elastic fibres were visualised using Hart's staining of sections of frozen inflated lungs obtained from 11 COPD stage 4 patients and three donor lungs. Compared with donors, non-COPD and stage 2-3 COPD, elastin mRNA expression was significantly increased in very severe COPD lungs (12-fold change), and localised in situ hybridisation induced elastin expression to alveolar walls. Compared with donors, alveolar elastic fibres also comprised a greater volume fraction of total lung tissue in very severe COPD lungs (p<0.01), but elastic fibre content was not increased per lung volume, and desmosine content was not increased. The present study demonstrates enhanced alveolar elastin expression in very severe COPD. The efficiency of this potential repair mechanism and its regulation remain to be demonstrated.

Alternative sequences of thyrotropin and free thyroxine assays for routine thyroid function testing. Quality and cost.

BACKGROUND: Current guidelines and practices for thyroid function testing are strongly affected by the usually higher patient billing charges and Medicare reimbursement for thyrotropin (TSH) vs free thyroxine (FT4) tests, despite their comparable direct costs. OBJECTIVE: Due to recently reduced laboratory costs, to reexamine the effectiveness and cost of alternative test sequences. METHODS: Alternative test sequences involve using the TSH test first, followed, if the TSH test result is abnormal, by the FT4 test; the FT4 test first, followed by the TSH test; and doing both tests together. We applied these strategies to consecutive patients referred for any thyroid function test to a health maintenance organization, a multispecialty fee-for-service group, a military hospital, and a commercial laboratory. Effectiveness was determined from a literature review. The cost was determined from direct costs and the distribution of diagnostic categories. RESULTS: The TSH and FT4 tests have similar sensitivities for detecting clinical hyperthyroidism and hypothyroidism. The TSH test detects subclinical function, and it monitors thyroxine treatment better; the FT4 test detects central hypothyroidism, and it monitors rapidly changing function better. Direct costs for both were equal, but charges for the TSH test were higher. The average direct cost per patient, starting with the FT4 test, was $4.61; starting with the TSH test, $5.90; and starting with both tests together, $6.50. Medicare reimbursements correlated poorly with costs. CONCLUSIONS: Starting with the TSH test and reflexing to the FT4 test provides a better first-line all-purpose sequence than the reverse. In managed care settings, the slightly higher direct cost of this approach is offset by greater clinical effectiveness. In fee-for-service settings, cost differences can be nearly eliminated by equalizing TSH and FT4 charges to reflect current direct-cost realities. Obtaining both tests together overcomes the disadvantages of each at a slightly higher direct cost.

Congenital atransferrinemia. A case report and review of the literature.

A four-year-old Polynesian girl with a two-year history of severe microcytic, hypochromic anemia (which was refractory to iron therapy) had a decreased beta-globulin fraction on serum protein electrophoresis, resulting from the absence of the transferrin (TRF) band. Subsequent assays for TRF showed a level below the detectable range. Liver biopsy revealed significant deposition of hemosiderin within hepatocytes and Kupffer cells, in addition to early fibrosis. Two bone marrow aspirates were hypercellular, with decreased myeloid-erythroid ratios. This case represents the eighth reported example of congenital atransferrinemia, a rare, apparently autosomal recessive disease.

Cavernous hemangioma of testis causing acute testicular infarction.

The sixth case of cavernous hemangioma of the testis is reported. The patient presented with acute testicular infarction, consistent with the tendency of this benign tumor to cause testicular atrophy. The importance of this tumor is in the differential diagnosis of malignant testis tumor.

Morphometric changes in the human pulmonary acinus during inflation.

Despite decades of research into the mechanisms of lung inflation and deflation, there is little consensus about whether lung inflation occurs due to the recruitment of new alveoli or by changes in the size and/or shape of alveoli and alveolar ducts. In this study we use in vivo (3)He lung morphometry via MRI to measure the average alveolar depth and alveolar duct radius at three levels of inspiration in five healthy human subjects and calculate the average alveolar volume, surface area, and the total number of alveoli at each level of inflation. Our results indicate that during a 143 ± 18% increase in lung gas volume, the average alveolar depth decreases 21 ±5%, the average alveolar duct radius increases 7 ± 3%, and the total number of alveoli increases by 96 ± 9% (results are means ± SD between subjects; P < 0.001, P < 0.01, and P < 0.00001, respectively, via paired t-tests). Thus our results indicate that in healthy human subjects the lung inflates primarily by alveolar recruitment and, to a lesser extent, by anisotropic expansion of alveolar ducts.

Imaging alveolar-duct geometry during expiration via ³He lung morphometry.

Acinar geometry has been the subject of several morphological and imaging studies in the past; however, surprisingly little is known about how the acinar microstructure changes when the lung inflates or deflates. Lung morphometry with hyperpolarized (3)He diffusion MRI allows non-destructive evaluation of lung microstructure and acinar geometry, which has important applications in understanding basic lung physiology and disease. In this study, we have measured the alveolar and acinar duct sizes at physiologically relevant volumes by (3)He lung morphometry in six normal, excised, and unfixed canine lungs. Our results imply that, during a 37% decrease in lung volume, the acinar duct radius decreases by 19%, whereas the alveolar depth increases by 9% (P < 0.0001 and P < 0.05, respectively via paired t-tests with a Bonferroni correction). A comparison to serial sections under the microscope validates the imaging results and opens the door to in vivo human studies of lung acinar geometry and physiology during respiration using (3)He lung morphometry.

Quantitative assessment of lung microstructure in healthy mice using an MR-based 3He lung morphometry technique.

The recently developed technique of lung morphometry using hyperpolarized (3)He diffusion magnetic resonance (MR) (Yablonskiy DA, Sukstanskii AL, Woods JC, Gierada DS, Quirk JD, Hogg JC, Cooper JD, Conradi MS. J Appl Physiol 107: 1258-1265, 2009) permits in vivo study of lung microstructure at the alveolar level. Originally proposed for human lungs, it also has the potential to study small animals. The technique relies on theoretical developments in the area of gas diffusion in lungs linking the diffusion attenuated MR signal to the lung microstructure. To adapt this technique to small animals, certain modifications in MR protocol and data analysis are required, reflecting the smaller size of mouse alveoli and acinar airways. This is the subject of the present paper. Herein, we established empirical relationships relating diffusion measurements to geometrical parameters of lung acinar airways with dimensions typical for mice and rats by using simulations of diffusion in the airways. We have also adjusted the MR protocol to acquire data with much shorter diffusion times compared with humans to accommodate the substantially smaller acinar airway length. We apply this technique to study mouse lungs ex vivo. Our MR-based measurements yield mean values of lung surface-to-volume ratio of 670 cm(-1), alveolar density of 3,200 per mm(3), alveolar depth of 55 µm, and mean chord length of 62 µm, all consistent with published data obtained histologically in mice by unbiased methods. The proposed technique can be used for in vivo experiments, opening a door for longitudinal studies of lung morphometry in mice and other small animals.

Angioimmunoblastic lymphadenopathy with dysproteinemia. Complete remission with cisplatin-based chemotherapy.

Angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) is classified as a nonmalignant condition, yet the mortality associated with the disease rivals most malignancies. Although a leading standard text recommends prednisone as initial management, there has been increasing evidence that combination chemotherapy is the best initial treatment. The patient described here achieved a complete remission with cisplatin-based therapy but later died of pneumonia, perhaps because pathogens important in infections in AILD were not covered. Specific recommendations for management are discussed.

Immunoperoxidase localisation of fibronectin in glomeruli of formalin fixed paraffin processed renal tissue.

An indirect immunoperoxidase technique was used to demonstrate fibronectin in sections of routine formalin fixed paraffin embedded renal tissue. Previous exposure of the sections to a solution of pepsin (4 mg/ml) in 0.01 N HCl for 2 h at 37 degrees C was essential in order to demonstrate antigenicity of fibronectin previously masked by fixation and embedding procedures.

Disorganisation of intermediate filament structure in alcoholic and other liver diseases.

The distribution of Mallory body antigens JMB1 and 2 was examined in 82 human fresh diagnostic needle liver biopsies and 28 necropsies by the indirect immunoperoxidase technique using 2 monoclonal antibodies (anti-JMB1 and 2) against Mallory bodies. The JMB1 antigen was detectable in bile duct epithelium and in hepatocytes of histologically normal livers. It was also found in all Mallory bodies in various hepatic disorders. This antigen was markedly increased in the cytoplasm of all liver cells in acute alcoholic hepatitis superimposed on alcoholic cirrhosis, in most cases of acute alcoholic hepatitis, and in severe fatty infiltration of the liver with or without Mallory body formation. Mallory bodies contained this antigen but the cytoplasm of Mallory body containing cells lacked JMB1. In normal liver the JMB2 antigen was localised on the cytoplasmic intermediate filament network of hepatocytes and bile duct epithelium; and almost all Mallory bodies also contained this antigen but the adjacent cytoplasm of these cells lacked JMB2. In severe alcoholic liver disease these antigens could not be detected in large zones of hepatocytes even when these hepatocytes did not contain Mallory bodies. It is evident that there is disorganisation of intermediate filament constituents in severe alcoholic liver disease.

A new marker for human cancer cells. 3. Immunocytochemical detection of malignant cells in serous fluids with the Ca1 antibody.

The Ca1 antibody has been used in an immunocytochemical procedure on smears of cells recovered from 50 effusions from the pericardial, peritoneal, and pleural cavities. In 25 samples containing malignant cells, as assessed by conventional morphological criteria, this antibody distinguished malignant from non-malignant cells in 21 samples. The exceptions were 2 lymphomas and 2 out of 6 carcinomas of the lung. The Ca1 antibody also reacted with malignant mesothelial cells from 2 mesotheliomas, but not with reactive mesothelial cells. This antibody thus provides a new method for the identification of malignant cells in pericardial, peritoneal, and pleural effusions.

A new marker for human cancer cells, 2 immunohistochemical detection of the Ca antigen in human tissues with the Ca1 antibody.

The Ca1 antibody has been used in an immunohistochemical procedure to detect the Ca antigen in sections of tissues routinely embedded in paraffin wax. A representative sample of benign and malignant tumours from all the systems of the human body has been examined. The majority of malignant tumors express the Ca antigen. The exceptions are: prostatic carcinomas, testicular teratocarcinomas and seminomas, some sarcomas, some lymphomas, malignant brain tumours, neuroblastomas, and melanomas. The antigen is least readily detected in epithelial malignancies of the alimentary system, particularly of the colon. The Ca1 antibody does not react with any benign tumour. The only normal tissues that react specificity with this antibody are the epithelium of the fallopian tube and the transitional epithelium of the urinary tract. The Ca1 antibody also readily distinguishes malignant cells in smears of malignant effusions. These findings indicate that the Ca1 antibody may be useful in the diagnosis of malignancy in routine clinical practice where the morphological interpretation of the biopsy or cytological smear is in doubt.

Tunable liquid-crystal filter for solar imaging at the He i 1083-nm line.

A Lyot-Ohman filter for imaging near the solar He i 1083-nm line is described. Fast and continuous spectral tunability is provided by nematic liquid crystals. This solid-state filter has a free spectral range of 2.35 nm and a spectral resolution of 0.135 nm at the operating wavelength of 1083 nm. A wide-fielded design was used for both static and electro-optic retarder elements, facilitating use in fast imaging systems. A first-light He i image of the Sun is presented.

Comparison of standard culture methods, a shell vial assay, and a DNA probe for the detection of herpes simplex virus.

A nonradioactive, biotinylated herpes simplex virus (HSV) DNA probe, a shell vial (rabbit kidney cell) culture assay enhanced by a direct fluorescent (HSV monoclonal)-antibody stain at 16 to 20 h postinoculation, and conventional tube cultures with confirmation via HSV-specific (polyclonal antibody) immunoperoxidase assay were compared for 199 specimens. The predictive values of the positive results were 54.5% for the probe, 95.9% for the shell vial assay, and 100% for the conventional culture methods, while the predictive values of the negative tests were 68.1, 84.0, and 98.4%, respectively. We conclude that the DNA probe (sensitivity, 24.5%; specificity, 88.3%) and the shell vial assay (sensitivity, 66.2%; specificity, 98.4%) cannot be substituted for conventional tube culture techniques (sensitivity, 97.1%; specificity, 100%) in the routine identification of HSV in our laboratory.