Reference equations for the single-breath diffusing capacity.
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Biomedical subjects
Publications and source records attributed to J C Thornton.
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The ontogenic switch from fetal to adult hemoglobin could result from discontinuous events, such as replacement of fetal erythroid progenitor cells by adult ones, or gradual modulation of the hemoglobin program of a single progenitor cell pool. The former would result in progenitors at midswitch with skewed fractional beta-globin synthesis programs, the latter in a Gaussian distribution. For these studies, we obtained bone marrow from rhesus monkey fetuses at 141-153 d (midswitch). Mononuclear cells were cultured in methyl cellulose with erythropoietin, and single BFU-E-derived colonies were removed and incubated with [3H]leucine. Globin synthesis was examined by gel electrophoresis and fluorography. The beta-globin synthesis pattern of single fetal colonies was skewed, and did not fit a normal distribution. The fetal pattern resembled the pattern of an artificial mixture of fetal and adult progenitors, suggesting that the fetal progenitor pool could contain populations with different beta-globin programs. This non-Gaussian distribution in the progenitors of midswitch fetuses is consistent with a discontinuous model for hemoglobin switching during ontogeny.
Families of 338 male and 81 female shipyard workers (SYW), including 280 wives, 144 daughters, and 81 sons, were examined for diseases resulting from asbestos. The workers were initially exposed to asbestos at least 20 years prior to the study date. Radiographic signs of asbestosis (using standard criteria international Labor Office 1980) were found in 64% of 288 male SYW and 21% of 71 female SYW. After excluding those with any occupational exposure to asbestos, asbestosis prevalence was 11% in wives, 8% in sons, and 2% in daughters. Asbestos disease prevalence in workers and in wives increased with the number of years from initial exposure. Male SYW who had smoked had airway obstruction without volume loss. Nonsmokers had normal pulmonary functions. In SYW households prevalences of respiratory diseases, wheezing on physical examination, and symptoms of asthma and chronic bronchitis, exceeded those in the comparison (Michigan) population, even for the younger daughters and sons. These differences, and airway obstruction and distribution defects reported earlier were not explained by cigarette smoking or by asbestos exposure. Instead, they are tentatively ascribed to long-term exposure to ambient air pollution in Los Angeles.
Fifteen of 71 women (21.1%) who had worked in shipyards before May, 1961 had radiographic signs of asbestos disease. There were irregular opacities in the lung parenchyma in seven and pleural disease in eight, two of whom had pleural calcifications. The 71 women who volunteered to be studied had a mean age of 61.5 years. Chronic bronchitis was diagnosed in 21%, 71% had dyspnea on climbing two flights of stairs, and 42% had wheezing. These prevalences were 50% higher than in wives of shipyard workers. In 50 white women, mean values for expiratory flow rates, log (FEF25-75) and log (FEF75-85), were decreased for non-, ex- and current smokers as compared to normal nonsmokers. Ex-smokers and current smokers showed the greater effects. Diffusing capacity (DLCOsb) and alveolar volume (ALV) were also reduced in all three smoking categories. Comparison to a reference population without asbestos exposure showed that for current, ex- and nonsmoking subgroups, there were significant reductions in log (FEF25-75), DLCOsb, and ALV for nonsmokers, reductions in FEV1, log (FEV25-75), and log (FEF75-85) in ex-smokers, and reduced ALV in current smokers. These decreases may reflect a locality effect. Further studies are recommended.
Spirometric measurements of vital capacity and flow rates, thoracic gas volume, and single-breath diffusing capacity for carbon monoxide were obtained in 360 white women, 238 wives age 58 years and 122 daughters age 32 years of shipyard workers from the Long Beach area of southern California. The values for nonsmokers, exsmokers, and current smokers were compared with smoking-specific mean values, age- and height-adjusted, from a reference population in Michigan. The wives from Long Beach had significantly lower mid and terminal flows, single-breath diffusing capacity for carbon monoxide, and alveolar volume, except that single-breath diffusing capacity for carbon monoxide was not significantly lower in current smokers. Nonsmokers and ex-smokers showed significantly different values for one-second forced expiratory volume in addition to flow rates and single-breath diffusing capacity for carbon monoxide. Daughters showed significant reductions in single-breath diffusing capacity for carbon monoxide and alveolar volume, which are attributable to maldistribution of inspired gas. These data showed that a powerful factor has affected expiratory air flow and distribution of gas, resulting in altered single-breath diffusing capacity for carbon monoxide and alveolar volume in this population. The factor is additive with and resembles the effect of cigarette smoking, and it is postulated that this factor is oxidant air pollution.
The plasma 17 alpha-hydroxyprogesterone (17-OHP) concentration was determined in the basal state and 60 minutes after cosyntropin, 0.25 mg, in 139 patients with idiopathic hirsutism (IH) and polycystic ovarian disease (PCOD). Although there was an increased response of 17-OHP in subjects with PCOD when compared with IH subjects, in no instance was stimulated 17-OHP abnormal in the presence of normal basal 17-OHP. Two subjects with 21-hydroxylase (21-OH) deficiency were discovered; both demonstrated elevated basal levels of 17-OHP. We therefore conclude that routine adrenocorticotropic hormone testing is not a useful tool in detecting 21-OH deficiency in hyperandrogenic women.
A group of 339 male shipyard workers responded to an invitation via shipyards, unions, and news media to be studied for the presence of asbestosis and its functional effects. Of these, 288 were white or black, had begun working in shipyards at least 20 years earlier, and had satisfactory chest x-ray film findings; 257 underwent spirometric testing, and 199 had single-breath diffusing capacities for carbon monoxide (Dsb) determined. There were radiographic signs of asbestosis in 64 percent. Of these, 28 percent had parenchymal disease only, 37 percent had pleural disease only, and 35 percent had both. There was pleural calcification in 9 percent. In only 14 (8 percent) was the profusion of opacities greater than 1/1 by the International Labour Organization's criteria. Age was closely related to the duration of exposure to asbestos. Thus, 87 percent of the workers who had asbestosis were born from before 1900 to 1910, 70 percent of those born in 1911 to 1920 had asbestosis, 62 percent of those born in 1921 to 1930 had the disease, and 31 percent of those born in 1931 to 1940 had signs of asbestosis. Function in nonsmokers was not significantly different from the reference population except for alveolar volume; ex-smokers had significantly reduced forced expiratory volume in one second, flow rates, Dsb, and alveolar volume. The forced vital capacity and thoracic gas volume were normal. Shipyard workers who smoked resembled reference smokers except for significantly reduced alveolar volume. These shipyard workers had minimal to moderate asbestosis with much pleural disease and little functional impairment when compared to a smoking-specific reference population.
Four-pi whole body counting for the 1.46 meV photon of 40K has apparent advantages over single-crystal or two-pi counters in efficiency and in subject geometry independence. However, our studies of obese populations have disclosed a systematic undermeasurement of 40K, suggesting that nonhomogeneous K distribution results in systematic undercounting of 40K. In the current study 42K, emitting a 1.52 meV photon, was used in 109 volunteers ranging from 50 to 181 kg, and multiregression covariance analysis was applied to develop correction formulas based on anthropometrics. These corrections quantitatively account for the unappreciated loss of 40K and 42K photons in annular adipose tissue that surrounds the lean body, in which most K+ is concentrated. The correction ranges from 1 to 28% and is a linear (although different) function of weight in both sexes. Thus corrected, body potassium measurements, taken in conjunction with exchangeable sodium and water measurements, provide estimates for whole body osmolality that match measured serum values. Such a quantitative accounting for previously "lost" cation in 58 subjects provides independent evidence for the appropriateness and accuracy of the correction. With this correction, body potassium was recalculated in the 1,492 adult members of a previously reported group of 3,083 subjects.
The development of hepatocellular carcinoma (HCC) is probably related to infection with hepatitis B virus (HBV). Hepatocytes in livers of patients with HCC have been reported to show putative preneoplastic changes such as hyperplasia, dysplasia, or adenomatous regeneration. To determine quantitatively whether these morphologic changes are associated with HBV-infected cells, the authors performed morphometry of hepatitis B surface antigen (HBsAg)-positive hepatocytes in the nontumorous portion of 10 livers with HCC and in 10 livers without HCC. The diameter of nuclei and cytoplasm of HBsAg-positive hepatocytes was measured after demonstration of HBsAg by the peroxidase-antiperoxidase method. As controls, HBsAg-negative hepatocytes in the same liver sections were measured as well as hepatocytes of 20 age-matched HBsAg-negative patients with normal liver or alcoholic cirrhosis. HBsAg-positive hepatocytes exhibited significantly larger nuclei and a higher nucleocytoplasmic ratio than control hepatocytes. In addition, HBsAg-positive cells were often arranged in foci that consisted of two cell populations: hypertrophic (enlarged nuclei and nucleocytoplasmic ratio) and hyperplastic (two-cell-thick plates of small cells with a high nucleocytoplasmic ratio). While precancerous cells have been difficult to identify, these morphologic changes are frequently associated with the development of malignant neoplasia.
A thermolysin-like metalloendopeptidase, optimally active at a neutral pH, was identified in human serum. The enzyme cleaves the synthetic substrate glutaryl-Ala-Ala-Phe-2-naphthylamide at the Ala-Phe bond. Activity was determined by measuring the rate of formation of Phe-2-naphthylamide in a coupled enzyme assay in the presence of excess aminopeptidase M. 2-Naphthylamine released during the reaction was determined by a diazotization procedure. Enzyme activity is not affected by inhibitors of serine, thiol, or carboxyl proteases, but is sensitive to inhibition by metal chelators such as EDTA and o-phenanthroline. Dialysis against EDTA leads to loss of activity, which can be fully restored by zinc and cobalt ions. The serum enzyme closely resembles a membrane-bound metalloendopeptidase (EC 3.4.24.11) abundant in lung, spleen, and kidney in that both enzymes are inhibited by the same active-site-directed inhibitors. In addition, an antiserum obtained against the metalloendopeptidase from rabbit kidney shows strong cross-reactivity with the serum enzyme. Metalloendopeptidase activity was measured in 150 controls and in 95 patients with sarcoidosis; the two groups had significantly different enzyme activities (p less than 0.001). The mean enzyme activity in the sarcoidosis group was more than threefold higher than that of the control group. The mean enzyme activity for patients with active disease was more than double that of patients with inactive disease and more than four times that of controls (p less than 0.001). This is noteworthy because angiotensin converting enzyme, a zinc-dipeptidyl carboxypeptidase with a mechanism of action similar to that of the metalloendopeptidase, has also been reported to be increased in the serum of patients with active sarcoidosis. Enzyme activity in patients with active tuberculosis, primary pulmonary neoplasms, and idiopathic interstitial pulmonary fibrosis did not differ significantly from that of controls.
In a prospective study of 15 spouses of women with advanced breast carcinoma, lymphocyte stimulation responses to phytohemagglutinin, concanavalin A, and pokeweed mitogen were significantly suppressed during the first two months following the death of a spouse compared with prebereavement levels. A highly significant suppression was seen as early as one month after bereavement. No differences were found in total lymphocyte or B- or T-cell numbers. An intermediate level of mitogen responsivity was found during the four- to 14-month period after bereavement. Suppressed immunity following the death of a spouse may be related to the increased morbidity and mortality associated with bereavement.
One hundred fifty-three midtrimester fetuses obtained from normal pregnancies terminated for nonmedical reasons were studied to establish normal standard measurements. Mean, standard deviation, range, and percentiles of body weight, foot length, crown-rump length, biparietal diameter, cardiac weight, thickness of ventricles, and ventricular septum were derived by computer analysis. Statistical analysis showed no sex difference. Equations for predicting body weight, cardiac weight, and septal thickness were derived with the use of fetal age and biparietal diameter as variables. The mean ratio of septal to left ventricular wall thickness was 1.14 +/- 0.34; a ratio of 1.3 or greater was found in 25% and a ratio of 1.5 or greater in 10% of this cohort. The results are at variance with the reported high incidence of septal hypertrophy seen in normal developing fetal hearts. We suggest that septal hypertrophy, ratio of 1.5 or greater, may reflect disturbances in fetal or placental circulation and warrants careful monitoring of the pregnancy.
Resting metabolic rate (RMR) was measured in 154 women and 48 men before the beginning of a weight reduction program. In both sexes there were significant univariate correlations between RMR and fat-free mass, body fat, weight, fat cell weight, and fat cell number (from total body water). Women also showed significant correlations between RMR and fat cell number (from total body potassium), free triiodothyronine index, and fasting and postglucose insulin levels. Multiple regression analysis showed that both fat-free mass and fat cell weight and number were significant predictors of RMR. The contribution of fat-free mass was three to five times greater per kg than that of body fat. There was no significant contribution of thyroid hormones or insulin to the prediction of RMR. Fat cell number and fat cell weight were significant predictors of RMR, whether determined from body water, body potassium, or a formula using both water and potassium. There was no significant difference in regression coefficients between men and women. Thus the difference in RMR between the sexes is probably caused by the higher proportion of fat-free mass in men. The effect of age was small and not statistically significant.
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In an attempt to identify health effects associated with low-level lead exposure, 45 cable-manufacturing workers underwent clinical examinations in a cross-sectional study. Thirteen workers were in direct contact with lead-containing stabilizers, while 31 were only indirectly exposed. The directly exposed had a higher prevalence of reported neurological and gastrointestinal symptoms than those with low or insignificant lead exposure. None of the directly exposed had blood lead levels exceeding 60 micrograms per 100 ml. The clinical symptoms correlated with blood lead and zinc protoporphyrin. However, when the data were subjected to hierarchical log-linear modeling, a partial association was found between zinc protoporphyrin and symptoms, but not between blood lead and symptoms. The data suggest that non-specific neurological and gastrointestinal symptoms may occur at relatively low blood lead and zinc protoporphyrin levels, and that measurement of zinc protoporphyrin and exploration of clinical symptoms are valuable components in lead screening programs.
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In this study of the delivery of outpatient psychiatric care to Medicaid patients at all 29 free-standing psychiatric clinics and at six hospital clinics in New York City, the authors found that nonphysician mental health workers provided much direct patient care: diagnosis and identifying data, necessary for reimbursement, were always included in records whereas mental status and medical history were poorly documented; and nonphysicians in hospitals generally surpassed physicians in the latter two areas. An additional observation was that attitudes of mental health workers toward certain diagnostic and ethnic groups may be inferred from the selective completeness of their psychiatric record keeping.
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