Cytomegalovirus pneumonitis after cardiac transplantation.

To evaluate the incidence and clinical features of cytomegalovirus (CMV) pneumonitis after cardiac transplantation, we identified 27 (16%) of 171 consecutive recipients in whom CMV pneumonitis was confirmed by strict diagnostic criteria. Cytomegalovirus pneumonitis occurred in 6 (30%) of 20 patients treated with azathioprine and prednisone, and 8 (25%) of 32 patients treated with azathioprine, cyclosporine, and prednisone, but only 13 (11%) of 119 patients treated with cyclosporine and prednisone. The incidence of CMV pneumonitis was not related to recipient preoperative CMV titers or to postoperative cardiac rejection, but there was a trend toward increased CMV pneumonitis in patients who received organs from CMV-positive donors. Mean onset of CMV pneumonitis was 2.9 +/- 1.6 (SD) months after transplantation. In the azathioprine-prednisone group, CMV was always associated with at least one other respiratory pathogen (Aspergillus, n = 5; Pneumocystis carinii, n = 2). In the two cyclosporine groups, CMV was either the sole respiratory pathogen (n = 9), or associated with P carinii (n = 11). Roentgenographically, diffuse bilateral hazy pulmonary opacities were present in 19 (70%) of 27 patients, but focal subsegmental opacity (26%), small pleural effusion (26%), and lobar consolidation (7%) were also observed. When bronchoscopy was performed, bronchoalveolar lavage was the most sensitive technique for detecting CMV (72%), whereas transbronchial biopsy (39%) and combined washings and brushings (33%) were relatively insensitive techniques. Respiratory failure and death occurred in 52% and 44%, respectively, of patients with CMV pneumonitis. In this population of immunocompromised hosts: (1) CMV pneumonitis, alone or with other respiratory pathogens, was a major cause of morbidity and mortality; (2) localized roentgenographic opacity did not exclude CMV pneumonitis; (3) bronchoalveolar lavage was the most sensitive bronchoscopic technique for detecting CMV pneumonitis.

Precautions in familial transmissible dementia: including familial Alzheimer's disease.

Recent studies suggest that some cases of familial Alzheimer's disease may be associated with a transmissible dementia. Animal experiments show that presymptomatic carriers of "slow virus" agents can transmit disease. Because of these findings, we have extended the precautions previously delineated to include those at risk of acquiring transmissible dementia, specifically, to the descendants of those affected with familial Alzheimer's disease or familial Creutzfeldt-Jakob's disease. Blood donation from such persons may pose a danger, because transmissible spongioform encephalopathy has been passed from animal to animal by blood serum and by the WBC layer of frozen whole blood.

Studies in aging of the brain: IV. Familial Alzheimer disease: Relation to transmissible dementia, aneuploidy, and microtubular defects.

Alzheimer disease was transmitted in a pattern consistent with an autosomal dominant trait in three families. This brings to 50 the number of such families reported. In one of our families, one patient had histologically confirmed Alzheimer disease, whereas her sister had proved spongiform encephalopathy. Other data suggest a link between familial Alzheimer disease and transmissible dementia. Alzheimer disease is associated with abnormal neurofibrillary structures, Down syndrome, and abnormal numbers of chromosomes in lymphocytes (aneuploidy). These observations are consistent with a disorder in the physiology of tubular-filamentous structures involving different cell types.

Clinical clues to the cause of Addison's disease.

Tuberculosis and other potentially treatable diseases remain important causes of adrenal insufficiency. Knowledge of the cause of adrenal destruction, although often difficult to ascertain clinically, is necessary for appropriate management. Clinical data are reviewed in eight patients with Addison's disease who underwent computed tomographic scanning and in 31 additional patients with Addison's disease in whom autopsy was performed. Seven of eight patients (87 percent) with tuberculous Addison's disease of no greater than two years' duration had enlarged glands whereas patients with longer duration of disease had smaller or normal-sized glands. Adrenal enlargement was also found in five of six (87 percent) subjects with carcinomatous replacement of the adrenal glands. The adrenal glands were small or undetectable in each of 16 patients with idiopathic Addison's disease. Adrenal calcification was found in nine of 17 (53 percent) tuberculous patients and was not found in any of the 22 other patients. Duration of adrenal disease, adrenal size on computed tomographic scanning, and presence of adrenal calcification were useful clues to the cause of Addison's disease.

Carcinoma of the lung after heart transplantation.

We have recently noted an unexpected high incidence of lung cancer in our population of cardiac allograft recipients. We conducted a retrospective review of cardiac transplantation at our institution to investigate the incidence, clinical course, and outcome of patients who developed lung cancer following heart transplantation. Nine patients--each with a history of smoking at 30 pack-years--developed lung cancer following heart transplantation, for an incidence of 1.56% of patients at risk. Eight of the patients were male > or = 50 years of age, representing 3.3% of the male transplant recipients in this age group. The interval from transplantation to diagnosis clustered around 3-5 years after transplantation, but in two instances (22%), a neoplasm was discovered within 6 months of transplantation. Almost half of the cancers were discovered incidentally, despite routine radiographic surveillance. Seven of 9 (78%) patients had stage IV disease at presentation. Median survival after diagnosis was 3 months, and five of the seven patients who died survived less than 4 months after diagnosis. We conclude that cardiac transplant recipients are at increased risk for development of lung cancer. Patients with a moderate to heavy smoking history might well be advised to undergo chest CT scanning in an aggressive search for occult lung cancer before cardiac transplantation is considered further. Finally, despite frequent radiologic examinations, these lung cancers are often diagnosed incidentally, are far advanced at the time of diagnosis, are not surgically resectable, and are poorly responsive to adjuvant therapy.

Increased aneuploidy in Alzheimer disease.

The purpose of this study was to determine if cytogenetic changes are present in Alzheimer disease, one of the presenile dementias. The chromosomes of three groups of people were studied: 1) sporadic cases of Alzheimer disease (eight cases), 2) familial cases of Alzheimer disease with affected individuals in at least two generations of their families (five cases), and 3) currently unaffected siblings of the affected individuals in these families (nine cases). One hundred cells per individual were examined using GTG banding to allow chromosome identification. A statistically significant increase in aneuploidy was found in five of eight patients in group 1 (P less than 0.05) and in each of five patients in group 2 (P less than 0.001) when compared with the rate of aneuploidy in age- and sex-matched controls. In addition, two individuals in group 3 exhibited a significant increase in aneuploidy over the control group, raising the possibility that finding increased aneuploidy may allow one to anticipate the clinical expression of the disease state.

Enhanced respiratory muscular function in normal adults after lessons in proprioceptive musculoskeletal education without exercises.

A subjective sense of enhanced ease of breathing has been described after instruction in the Alexander technique of proprioceptive musculoskeletal education (awareness and voluntary inhibition of personal habitual patterns of rigid musculoskeletal constriction). We investigated the effects of AT instruction on respiratory function in healthy adult volunteers (group 1, ten subjects), who received 20 private AT lessons at weekly intervals. Spirometric tests, including maximum static mouth pressures, were assessed before and after each course of lessons. Healthy control subjects, matched for age, gender, height, and weight (group 2, ten subjects), without instruction, were tested over a similar interval. Group 1 showed significant increases in PEF (9 percent, p less than .05), MVV (6 percent, p less than .05), MIP (12 percent, p less than .02), and MEP (9 percent, p less than .005) (paired Student's t testing). Group 2 showed no significant changes. Possible mechanisms for the changes in group 1 include increased length and decreased resting tension of muscles of the torso, which in turn may increase their strength, increase thoracic compliance, and/or enhance coordination. We conclude that AT musculoskeletal education may enhance respiratory muscular function in normal adult subjects.

Reversible pulmonary artery obstruction in a patient with bronchogenic carcinoma. Diagnosis by two-dimensional and Doppler echocardiography.

Neoplastic invasion of the pulmonary arteries, although common, rarely results in obstruction to right ventricular outflow. We report an unusual case of severe pulmonary hypertension, right ventricular dilatation, and righ ventricular dysfunction resulting from pulmonary arterial compression by bronchogenic carcinoma. The diagnosis was made by two-dimensional and Doppler echocardiography and supported by computed tomographic findings. Echocardiography was used to follow the patient's response to therapy and documented the subsequent resolution of pulmonary arterial obstruction.

Pulmonary tuberculosis after lung transplantation.

During a 5-year study period, we diagnosed pulmonary tuberculosis in two (2%) of 94 lung and heart-lung transplant recipients. Each infection occurred 3 months after bilateral lung transplantation in the presence of evidence implicating donor-to-recipient transmission of the pathogen. The radiographic patterns of pulmonary tuberculosis were subtle: narrowing of the middle lobe bronchus of the right lung caused by an endobronchial granulomatous mass (n = 1) and a focal cluster of small nodules in the upper lobe of the left lung and small bilateral pleural effusions (n = 1). Each patient achieved complete clinical and radiographic response after antituberculous therapy. We conclude that Mycobacterium tuberculosis may be transmitted directly by a donor lung and may involve bronchial mucosa, pulmonary parenchyma, and pleura.

Acute asthma. Admission chest radiography in hospitalized adult patients.

The utility of admission chest radiography has been controversial in the management of adult patients admitted to the hospital with acute asthma. We reviewed the impact of admission chest radiography on in-hospital management of 54 adult patients with acute asthma. Each patient was admitted after a failed 12-h course of bronchodilator therapy in the emergency ward. Major radiographic abnormalities were found in 20 (34 percent) of 58 occasions. These abnormalities included focal parenchymal opacities, IIM, enlarged cardiac silhouette, pulmonary vascular congestion, new solitary pulmonary nodule and pneumothorax. Subsequent antibiotic use correlated with radiographic focal opacities or IIM, even in afebrile patients, but did not correlate with elevated blood leukocyte count. Based on the evidence of in-hospital alteration of management independent of elevated blood leukocyte count and body temperature, we recommend that chest radiographs be obtained for all adult patients admitted because of acute asthma.

Radiologic assessment of pulmonary arterial pressure and blood volume in chronic, diffuse, interstitial pulmonary diseases.

Chronic, diffuse, interstitial pulmonary diseases may cause an increase in mean pulmonary arterial pressure (PAP) and a decrease in pulmonary blood volume (PBV). We compared 12 cardiovascular and three parenchymal assessments on plain chest radiographs with values of PAP and PBV obtained during cardiac catheterization in 29 patients with such diseases (progressive systemic sclerosis 20, sarcoidosis six, miscellaneous three) and normal pulmonary venous pressures. PAP ranged from 10 to 40 torr (mean 19, SD +/- 7), PBV from 6.4 to 10.8% of total blood volume (mean 8.4, SD +/- 1.2). PBV was significantly related to eight radiologic variables. PAP was significantly related to the severity of parenchymal disease and size of the central pulmonary arteries, both of which were assessed radiologically. Diversion of blood flow to upper zones was significantly related to restriction of the pulmonary vascular bed, but was not necessarily a sign of increased PAP. In general, pulmonary hemodynamic abnormalities appeared proportional to the radiologic severity of parenchymal disease.

The impact of routine chest radiography on the management of patients admitted from an emergency service.

Adult patients entering a hospital usually undergo a routine admission chest radiographic examination (RACXR). Recently, this practice has been questioned. The clinical course of 188 patients admitted to an adult medical service from the emergency area of an inner city hospital was assessed prospectively. Each of these patients underwent RACXR, ie, the only indication for the examination was admission to the hospital. Four subpopulations considered to be at high risk for treatment-altering radiographic abnormalities were defined prospectively: age of 65 years or older, cigarette smokers, altered mental status, and human immunodeficiency virus (HIV) positivity. RACXR abnormalities were significantly more common in the subpopulations at high risk (104/127, 82%) than in the population at low risk (37/61, 61%) (P less than .01). Abnormalities on RACXR led to altered treatment in five (3%) of the 188 inpatients. Each of these five patients was a member of a subpopulation at high risk (5/127, 4%). Because results suggest that various clinical considerations may affect the yield of RACXR, it is proposed that a blanket recommendation to eliminate RACXR is premature.

Nodular bleomycin toxicity.

Pulmonary interstitial fibrosis, a well-known toxic effect of bleomycin therapy, usually presents radiographically as diffuse reticularity. The authors report an unusual case of biopsy-proven bleomycin toxicity that presented as pulmonary nodules mimicking metastatic tumor. The histologic findings resembled those seen in the diffuse form of toxicity but notably also included foci of bronchiolitis obliterans.

A general natural-language text processor for clinical radiology.

OBJECTIVE: Development of a general natural-language processor that identifies clinical information in narrative reports and maps that information into a structured representation containing clinical terms. DESIGN: The natural-language processor provides three phases of processing, all of which are driven by different knowledge sources. The first phase performs the parsing. It identifies the structure of the text through use of a grammar that defines semantic patterns and a target form. The second phase, regularization, standardizes the terms in the initial target structure via a compositional mapping of multi-word phrases. The third phase, encoding, maps the terms to a controlled vocabulary. Radiology is the test domain for the processor and the target structure is a formal model for representing clinical information in that domain. MEASUREMENTS: The impression sections of 230 radiology reports were encoded by the processor. Results of an automated query of the resultant database for the occurrences of four diseases were compared with the analysis of a panel of three physicians to determine recall and precision. RESULTS: Without training specific to the four diseases, recall and precision of the system (combined effect of the processor and query generator) were 70% and 87%. Training of the query component increased recall to 85% without changing precision.

Right ventricular obstruction in aortic dissection: a mechanism of hemodynamic collapse.

The main and right pulmonary arteries may be compressed by the false lumen of a type I aortic dissection. We report a 73-year-old women with a dissection of the aorta in whom echocardiographic examination revealed acute pulmonary arterial compression causing right ventricular failure and hemodynamic collapse.

The lateral chest radiograph in the assessment of nonpulmonary health and disease.

The lateral chest radiograph contains a wealth of data on the status of the thoracic cage, pleura, heart, pericardium, bronchi, and upper abdomen. The appearances of slightly oblique projections deviating from the "true" lateral projection are reviewed. Careful attention to these common variations of projection is advocated.

The effects of minor degrees of obliquity on the lateral chest radiograph.

Minor degrees of obliquity affect the appearance of the lateral chest radiograph. For 100 normal subjects we compared findings on three left lateral projections: the "straight lateral", rotation of the subject's right side 10 degrees anterior ("right anterior"), and rotation of the patient's right side 10 degrees posterior ("right posterior"). A number of structures appeared generally best seen in the "right anterior" lateral projection, less well seen in the "straight posterior" lateral projection and least well seen in "right posterior" lateral projection. These structures were the epicardial fat stripe and pericardial line, the anterior margin of the ascending aorta, the hilar vessels, the origins of the upper lobe bronchi, and the posterior wall of the bronchus intermedius. The heart appeared largest in the "right anterior" lateral view, while in the "right posterior" lateral view it appeared smallest (whether assessed subjectively or by measurement of posterior left ventricular overlap of the inferior vena cava). Similarly, the hilar vascular shadows and major bronchi were most prominent when rotated apart in the "right anterior" projection and least prominent when more nearly superimposed in the "right posterior" projection. Slight rotation showed no significant effect on the anteroposterior diameter of the trachea, the width of the left pulmonary artery, or the diameters of the upper lobe bronchi. The azygos vein and a well visualized posterior tracheal band were seen in a few patients. They tended to be best and most frequently seen in the "right posterior" lateral view. Either obliquity tended to improve delimeation of the anterior pleural margins and the costophrenic angles. This was also true for the interlobar fissures, but confusing superimposition shadows were less likely in the "right anterior" than the "right posterior" lateral radiograph.

Studies in metachromatic leukodystrophy. XIV. Purification and subunit structure of human liver arylsulfatase A.

Arylsulfatase A was purified to apparent homogeneity from normal human livers obtained at autopsy. According to gel electrophoresis in sodium dodecyl sulfate, purified arylsulfatase A consistently contained two subunits of slightly different sizes: approximately 69 000 and 57 000 daltons, but were not present in stoichiometrically equal amounts. Peptide maps of the entire enzyme and of the two individual subunits showed that the two polypeptides share similar if not identical sequences. These observations raise the possibility that the smaller polypeptide might be derived from the larger one. The sensitive peptide mapping procedures employed will make feasible future studies with the abnormal enzyme found in metachromatic leukodystrophy.

Pulmonary sarcoidosis: could mycoplasma-like organisms be a cause?

The etiology of sarcoidosis is unknown but an unusual bacterial agent is possible. Mycoplasma-Like Organisms [MLO] are obligate intracellular cell wall deficient bacteria with a distinctive ultrastructural appearance. MLO are a common cause of various transmissible plant diseases. Despite over 25 years of effort MLO remain uncultivated. Molecular biologic studies indicate MLO are only distantly related to extracellular cultivable mycoplasma. Diagnosis of MLO diseases is based chiefly on detection of the organisms in infected cells by electron microscopy. Recently MLO have been detected by electron microscopy within leucocytes in sterile inflamed aqueous and vitreous humor from patients with idiopathic chronic uveitis including sarcoidosis uveitis. Preliminary molecular biologic studies suggest that human MLO are quite closely related phylogenetically to plant MLO. Inoculation of human uveitis MLO into mouse eyelids produced chronic uveitis and lethal systemic granulomatous disease with MLO within leucocytes and endothelial cells in the disease sites. The MLO induced animal pulmonary disease resembled sarcoidosis. This report describes abnormal intracellular bodies consistent with MLO within leucocytes and endothelial cells adjacent to the granulomas in transbronchial biopsies from 9 corticosteroid untreated sarcoidosis patients versus none in 4 control lungs.

Studies in metachromatic leukodystrophy: XV. Purification of normal and mutant arylsulfatase A from human liver.

In this report we describe a method to purify both normal and abnormal (inactive) arylsulfatase A. The abnormal enzyme protein was isolated both from cases of late infantile and early juvenile forms of metachromatic leukodystrophy. Conventional protein isolation methods reported earlier were followed by size exclusion high-performance liquid chromatography in the final purification stages. Both the mutant enzyme and the normal enzyme had the same HPLC elution behavior. They thus appeared to self-associate in a similar pH-dependent fashion. Both could be followed by their reaction to a rabbit antibody to normal human arylsulfatase A. The amount of homogenous protein obtained from about 500 grams of liver was 300-400 micrograms.