Anaplastic astroblastoma-sarcoma in neurofibromatosis Type 1.

Astroblastoma is a distinctive brain tumor when its histologic features occur in pure form. More often, the tumor pattern is seen to emerge in infiltrative astrocytic tumors. The former are rare. Astroblastoma as a de novo component of gliosarcoma has not previously been described. Furthermore, astroblastoma has only once been reported to occur in the setting of neurofibromatosis Type I (NF1), a condition more often associated with pilocytic and diffuse or infiltrative astrocytic tumors. Herein, we describe a unique case of anaplastic de novo astroblastoma-sarcoma, in essence a variant of gliosarcoma, occurring in a 50-year-old female with documented NF1. Genetic study (fluorescence in situ hybridization) demonstrated no chromosomal losses or gains. Testing for abnormalities of chromosomes 7, 9, 10, 12, 17, 19 and 20, including the EGFR, p16, PTEN, MDM2 and NF1 gene regions, we found the tumor to exhibit a deletion of PTEN, monosomy 17 and gains of chromosomes 19 and 20q. The latter alterations, having been reported in astroblastoma, were noted in both tumor components, thus confirming the common origin of the glial and sarcomatous elements.

Assessment of alpha-1-antitrypsin deficiency heterozygosity as a risk factor in the etiology of emphysema. Physiological comparison of adult normal and heterozygous protease inhibitor phenotype subjects from a random population.

For plethysmographic studies of lung mechanics and measurement of pulmonary diffusing capacity, 62 subjects were drawn from a randomly selected population sample. Data obtained from the 24 subjects of heterozygous phenotype for alpha-1-antitrypsin deficiency (PiMZ) were compared by age group with data from 38 normal (PiM) subjects matched for sex, age, and smoking history. Comparison of mean values by age group for lung volumes, diffusing capacity, lung elastic recoil, maximum expiratory flow, and the occurrence of frequency dependence of dynamic compliance revealed no differences between phenotype groups. There was no evidence of an accelerated effect of aging among PiMZ subjects when compared with normal counterparts nor was there evidence of an increased effect of smoking. From these data it appears that the PiMZ phenotype per se is not a risk factor in the development of emphysema.

Connective tissue dysplasia in five new patients with NF1 microdeletions: further expansion of phenotype and review of the literature.

Approximately 5% of patients with neurofibromatosis type 1 (NF1) have deletions of the entire NF1 gene. The phenotype usually includes early onset, large number of neurofibromas, presence of congenital anomalies, cognitive deficiency, and variable dysmorphic features and growth abnormalities. Connective tissue abnormalities are not generally recognised as a part of NF1 microdeletion syndrome, but mitral valve prolapse, joint laxity, and/or soft skin on the palms have been reported in a few patients. We describe clinical findings in six newly diagnosed patients with NF1 microdeletions, five of whom presented with connective tissue abnormalities. A literature review of the clinical findings associated with NF1 microdeletion was also performed. Our report confirms that connective tissue dysplasia is common in patients with NF1 microdeletions. Given the potential for associated cardiac manifestation, screening by echocardiogram may be warranted. Despite the large number (>150) of patients with known NF1 microdeletions, the clinical phenotype remains incompletely defined. Additional reports of patients with NF1 microdeletions, including comprehensive clinical and molecular information, are needed to elucidate possible genotype-phenotype correlation.

Development of a D-FISH method to detect DEK/CAN fusion resulting from t(6;9)(p23;q34) in patients with acute myelogenous leukemia.

The t(6;9)(p23;q34)-DEK/CAN fusion occurs with an incidence of 1-5% in adult patients with acute myelogenous leukemia (AML) and tends to have an unfavorable prognosis at diagnosis. Due to the subtle appearance of this chromosome rearrangement, both initial detection and minimal residual disease (MRD) tracking by conventional karyotyping can be difficult. Unfortunately, no commercial or previously published fluorescence in situ hybridization (FISH) strategies exist for this recurrent anomaly. We have developed a highly sensitive assay using dual-color, double-fusion FISH (D-FISH), which can be used both for initial detection and MRD monitoring. We analyzed archived bone marrow samples from 15 patients with a previously identified t(6;9)(p23;q34) and 10 corresponding post-treatment samples. The results demonstrate that our D-FISH method effectively identified all abnormal samples, including a low-level MRD sample that was considered to be normal by conventional cytogenetic analysis. Normal value ranges were established from 30 negative controls to be < 0.6% when 500 interphase nuclei were analyzed. The development of this sensitive D-FISH strategy for the detection of the t(6;9)(p23;q34) adds to the AML FISH testing repertoire, and is effective in the detection of low-level disease in post-treatment samples in these patients.

Neonatal heelstick blood culture.

A new micro-heelstick blood culture technique was evaluated in 40 neonates who were believed to be clinically septic. Heelstick cultures were positive in 11 and peripheral venous cultures were positive in eight. All eight venous cultures had positive heelstick cultures. Heelstick blood cultures seem to be at least as sensitive as venous cultures.

Symptomatic arteriovenous malformation in infants less than 6 months of age.

The symptomatology and sequelae of symptomatic system arteriovenous (A-V) malformations in children less than 6 months old make an early diagnosis possible and early treatment mandatory. A group of 156 infants with systemic A-V malformations involving the CNS (81 infants), liver (61 infants), and lungs (14 infants) were studied to compare symptoms, diagnosis, treatment, and outcome. Congestive heart failure was present in 67% of the patients with CNS A-V malformations. Mortality among the patients with CNS A-V fistulas was 64%. Of those patients with hepatic A-V malformations 67% had abdominal masses, 48% congestive heart failure, and 55% died. Pulmonary A-V malformations presented with congestive heart failure 57%, cyanosis 43%, and resulted in a 43% mortality. Early combined medical and surgical therapy offered the best chance for a successful outcome.

Frequency dependent phase and amplitude differences between simulated mouth and pleural pressures during panting. Demonstration with a mechanical model.

A mechanical model was employed to examine phase and amplitude relationships between simulated pleural and mouth pressures during panting at different frequencies with and without lower airway obstruction and with rigid or flaccid extrathoracic airways. Results confirm the hypothesis that, in the presence of lower airways obstruction, compliant extrathoracic airways act as a shunt impedance. Consequently, mouth pressure changes may be out of phase with and underestimate changes in pleural pressure, affecting the measurement of thoracic gas volume.

Exercise-aggravated hypoxemia and orthodeoxia in cirrhosis.

A syndrome characterized by hypoxemia aggravated by exercise, orthodeoxia, hypocapnia, and evidence of hyperdynamic circulation, but otherwise normal indices of pulmonary air flow, volume, and distribution of ventilation has been observed as an infrequent complication of hepatic cirrhosis. An illustrative case is described, the features of which support the presence of a shunt or shunt-like mechanism consisting of low-resistance vascular communications within the lung. We suggest that this may represent the existence of a hepatopulmonary syndrome analogous to the hepatorenal syndrome.

Significance of intraindividual changes in maximum expiratory flow volume and peak expiratory flow measurements.

To examine criteria to assess significant changes of measurements derived from the forced expiratory vital capacity (FVC), and to examine changes in the peak expiratory flow (PEF) maneuvers, ten subjects were tested on approximately 30 occasions. Since mini Wright peak flow meters are increasingly used for clinical and research purposes, peak flow intraindividual variability and relations to FVC peak flow were examined, each set of tests consisting of five FVC maneuvers and one peak flow. Measurements on a pneumotachograph included FVC, (FEV1), maximum mid-expiratory flow (MMF or FEF25-75%), and instantaneous maximum expiratory flow after 50 and 75 percent expiration of the FVC. PEF measurements were derived using the mini Wright peak flow meter and the pneumotachograph. The coefficients of variation for the FVC measurements were greatest for maximum expiratory flow measurements and least for the FVC and FEV1. Maximum values from each set of tests reduced the variability. From these values, criteria and estimates were derived to evaluate significant intraindividual change. The PEF measurements were evaluated also to determine intraindividual changes. The coefficients of variation were only 2 percent to 14 percent. The peak flows obtained were shown to correlate well with the PVC peak flow.

Spirometric testing. Number of tests required and selection of data.

To address the questions of whether three or five maneuvers for forced vital capacity (FVC) should be required for adequate spirometric testing and whether the largest or mean values for FVC and the forced expiratory volume in the first second (FEV1) should be used for analysis, we analyzed spirometric data obtained from approximately 3,000 people for each of three consecutive years. The following four algorithms for selection of data were tested: (1) the average of the best two of five measurements; (2) the average of the best two of the first three; (3) the best of five; and (4) the best of the first three. There were no significant differences between any two algorithms within a given year and no differences between any two years for any algorithm. We conclude that there is little to be gained by requiring more than three maneuvers for FVC or in using values other than the largest FEV1 and FVC.

Assessment of air vs helium-oxygen flow-volume curves as an epidemiologic screening test.

Air and helium-oxygen maximum expiratory flow-volume curves were employed in an epidemiologic field study to assess the utility of density dependence as a screening test. Of 1,584 subjects tested, only 54.1 percent were able to perform the test with vital capacities for the two gases that agreed to within 5 percent. Subjects unable to perform the test properly tended to be older, with a greater prevalence of ventilatory function abnormalities and respiratory problems, than those who could perform the test. There was poor concordance between density dependence, or lack thereof, and standard ventilatory function measurements or evidence of respiratory disease. Under field survey conditions, the test of density dependence did not appear to be a useful screening tool.

Subclinical effects of cigarette smoking. A five-year follow-up of physiologic comparisons of healthy middle-aged smokers and nonsmokers.

Measurements of ventilatory function, lung elastic recoil, diffusing capacity, and distribution of ventilation were obtained on healthy middle-aged cigarette smokers and nonsmokers on two occasions five years apart in order to assess the effects of smoking and the change which may occur over this five-year interval. Subjects were drawn from a randomly selected sample of the population of Tucson, AZ. Exactly the same protocol, methods, and equipment were employed in both studies. Although very few of these healthy subjects had abnormal function, there were significant differences in most indices of function between smokers and nonsmokers. However, we could discern no difference between smokers and nonsmokers in change in function over five years. It appears that, in smokers who remain free of serious respiratory trouble, there are subtle changes which accumulate over the years and which are too gradual to detect over a five-year interval.

Subclinical effects of smoking. Physiologic comparison of healthy middle-aged smokers and nonsmokers and interrelationships of lung function measurements.

Measurements of ventilatory function, distribution of ventilation, diffusing capacity, and lung mechanics were made on healthy middle-aged smokers and nonsmokers drawn from a randomly selected population in order to assess the effects of cigarette smoking and the interrelationships of the several indices of lung function. Although very few subjects had abnormal function, there were significant differences in most indices of function between smokers and nonsmokers. For the total group studied, there were significant correlations between various indices of function. A significant proportion of the variance in diffusing capacity and in diffusing capacity per liter of lung volume can be accounted for by an index of lung recoil which may, in turn, be related to size of terminal air spaces.

Vectorcardiographic and blood pressure correlates of obstructive pulmonary diseases in a community population.

Vectorcardiography was performed on 2,449 subjects, aged six years and older, in the Tucson (Ariz) Epidemiological Study of Airway Obstructive Diseases (AOD), 95 percent of the white non-Mexican Americans in the stratified cluster population sample. The objectives were to confirm previous relationships and to determine if hypothesized changes in the vectorcardiogram (VCG) could predict AOD. Trained nurse technicians performed the VCGs, which were read and interpreted by a cardiologist. Vectorcardiographic results were broadly interpreted for abnormalities. Also, calculated vector means and angles were compared to standard questionnaire responses for medical history, to maximum expiratory flow-volume variables, and to values for blood pressure; these were all corrected for sex, age, height, weight, and the ponderal index. Values were expressed as percentages of predicted. Over 80 percent of the VCGs were found to be normal. Measured hypertrophy was related to disease; there were significantly more abnormalities in those with histories of heart disease, hypertension, arteriosclerosis, and AOD, when examined by types of ventricular hypertrophy and VCG-identified heart disease or hypertension; findings of AOD and heart disease were also correlated significantly. Of all the ventricular hypertrophy, right ventricular hypertrophy (RVH), type C, was confirmed to be the predominant type associated with decreased pulmonary function in all smoking groups. Systolic blood pressure was related to RVH, type A, and diastolic 4 and 5 blood pressure with RVH, types A and B. The vectors' magnitude and angles were related to abnormality of pulmonary function in those with and without heart disease and AOD.

Characteristics of asthma among elderly adults in a sample of the general population.

This article describes the characteristics and course of asthma among subjects who were older than 65 years at the time of enrollment in a longitudinal study of a general population sample. It was present in 3.8 percent of men and 7.1 percent of women. An additional 4.1 percent of men reported having "asthma," but they also had seen a physician for "emphysema" and had smoked significantly; their "asthma" diagnosis is regarded as highly questionable. They did not show the elevated rate of allergy skin test reactivity of high serum IgE levels that were characteristic of other asthmatics. Many of the elderly asthmatics (mean age, 72 years) had severe disease with marked ventilatory impairment. There was a close relationship between the severity of wheezing complaints and impairment of the FEV1. Of the 46 patients, 48 percent reported an onset before age 40 years. There was no relationship between severity and age of onset or duration of disease. A second diagnosis of "chronic bronchitis" was reported by 46 percent of the asthmatics, but this did not delineate a distinctive group with late-onset, smoking-related disease. Death rates in the asthmatics tended to be higher than in nonasthmatics (odds ratio, 1.9; CI, 0.998 to 3.70, after stratifying by sex). Over a mean follow-up of 7.44 years, most symptoms as well as the FEV1 remained relatively stable. Chronic productive cough did tend to remit (p less than 0.01), but this was noted in the nonasthmatics as well. We estimate that no more than 19 percent of the asthmatics went into complete remission during follow-up. Most of these had mild initial symptoms; there were no remissions in subjects with severe disease at the time of entry. We concluded that asthma in the elderly is not a rare disease and may be associated with severe symptoms and chronic airways obstruction. If severe, it rarely goes into complete remission but tends to remain a severe, disabling disorder.

A descriptive analysis of the growth and decline of the FVC and FEV1.

Using data obtained during the first four complete surveys of a general population sample (2,435 spirometric studies on 916 different asymptomatic nonsmoking subjects), we have derived mathematically continuous equations designed to describe the stages of growth, maturation, and subsequent decline in the forced expiratory volume in one second (FEV1) and the forced vital capacity (FVC). With this type of analysis, there appears to be a period from late childhood through adolescence in which maturation significantly increases FVC and FEV1 independent of growth, and a stage from late adolescence to the early or mid-30s in which there is relatively little change in these measurements. Progressive decline in FVC and FEV1 may not actually begin until the mid-30s. The mathematical formulae presented here were derived in a manner intended to describe biologic events and are not intended for use as prediction equations. The FEV1/FVC ratio appeared to be primarily a function of the FVC itself in young subjects. After the age of 33 years, FEV1/FVC also decreased with age, independent of the size of the FVC.

Interactions of smoking and immunologic factors in relation to airways obstruction.

The relationships of smoking, allergy skin test reactivity, and serum IgE to ventilatory function have been analyzed in 1,182 subjects from a general population sample. The study group consisted of subjects aged 35 or more who deny previous lung surgery, old tuberculosis, or a current diagnosis of heart disease in the absence of chronic bronchitis or emphysema. Impairment of the forced expiratory volume in one second (FEV1) shows a definite relationship to total serum IgE. However, this relationship is significant only for a low FEV1 which is accompanied by symptoms suggesting asthmatic or a chronic bronchitis type disease. Allergy skin test reactivity to a battery of common aeroallergens shows no overall relationship to FEV1. However, after accounting for total serum IgE, positive allergy skin tests tend to be associated with high rather than low FEV1 values. The findings suggest that some type of IgE which is not specific for aeroallergens but which is associated with smoking, may be important in the pathogenesis of the "chronic asthmatic bronchitis" syndrome.

Expiratory computed tomography for assessment of suspected pulmonary emphysema.

Results of computed tomography of the lung performed at two levels in upper lung zones at full inspiration and full expiration were compared with results of tests of ventilatory function, lung mechanics, and single breath carbon monoxide diffusing capacity in 64 subjects, many of whom had some form of airflow obstruction. From the CT scans, the mean percentage of pixels in the range -900 to -1,024 Hounsfield units, or pixel index, was determined for each subject. The highest correlations of pixel index with physiologic variables consistent with a diagnosis of emphysema were observed for CT taken at full expiration. In some subjects, the inspiratory CT would give a "false positive" for emphysema when the hyperaeration observed at inspiration was not observed at expiration. We believe that the CT scan taken at full expiration can effectively reveal the abnormal permanent enlargement of airspaces which defines emphysema and provides a noninvasive method of assessing lung morphology in the living human subject.

Surgical management of emphysema.

The history of surgery for the treatment of emphysema and its complications is long and complex and, with improved understanding of the pathophysiology, most procedures have been discarded. Present clear indications for surgery are mainly large or increasing bullae that result in compression of apparently good lung tissue, and complications of bullous emphysema such as pneumothorax and infection. With localized giant bullae the results of local resection can be as dramatic as the effects of pleural drainage for tension pneumothorax. Lobectomy should not be undertaken until bullae have been removed locally and application of positive pressure has failed to reveal any expandable lung tissue--a rare situation. Resection of small bullae generally has no effect on lung function. The indications for resection of large bullae in the presence of diffuse emphysema require careful individual study. In such cases even a small increment of function may be of great clinical benefit, and there is evidence that longevity can be increased. Finally, two-stage local drainage of tension bullae may be indicated in those rare cases in which open thoracotomy cannot be considered for other reasons.

Interpersonal perception and mode of resolution in marital conflict.

The present study examined the relationship between changes in couples' perceptions of each other during a conflictual interaction and their mode of conflict resolution. Thirty-three volunteer married couples were videotaped while recreating a conflictual interaction that had occurred previously. During a subsequent replaying of the videotape, husbands' and wives' verbal descriptions of perceptions of self and spouse were elicited at three different stages of the conflict, using a method for eliciting perceptions derived from Laing. Phillipson, and Lee's multiperspective interpersonal perception technique. The interpersonal perceptions of couples who resolved the conflict by engaging the issue at hand were contrasted with those of couples who resolved the conflict via avoidance. Statistically significant differences were found between the groups, suggesting that engaging the issue was associated with an increase in spouses' access to one another's interpersonal perceptions, whereas avoidance was associated with decreases in consensually valid perceptions. Substantive and methodological implications of the study are discussed.