Epidemiological findings of seasonal changes in mood and behavior. A telephone survey of Montgomery County, Maryland

Patterns of seasonal changes in mood and behavior in Montgomery County, Maryland, were evaluated in randomly selected household samples by lay interviewers using a telephone version of the Seasonal Pattern Assessment Questionnaire. The method for selecting the sample unit was random-digit dialing. We found that 92% of the survey subjects noticed seasonal changes of mood and behavior to varying degrees. For 27% of the sample seasonal changes were a problem and 4.3% to 10% of subjects, depending on the case-finding definition, rated a degree of seasonal impairment equivalent to that of patients with seasonal affective disorder. The seasonal pattern of "feeling worst" exhibited a bimodal distribution with a greater winter and a substantially lower summer peak (ratio, 4.5:1). Younger women who have a problem with seasonal changes and who feel worse on short days tended to exhibit the highest seasonality scores. It is apparent from our study that seasonal affective disorder represents the extreme end of the spectrum of seasonality that affects a large percentage of the general population. The influence of environmental factors on mood disorders and mood changes in the general population might provide valuable insight into pathogenesis, treatment, and prevention of affective illness.     

"Single-exposure" dual energy digital radiography in the detection of pulmonary nodules and calcifications

We studied the detectability of mineralized and non-mineralized simulated pulmonary nodules with dual energy digital radiography. "Soft tissue" and "bone" images (pixel size = 0.2 mm, 10 bits deep) were obtained with subtraction image processing after a single simultaneous exposure (100 kVp, 8 mAs, 17 mR skin exposure dose) of two storage phosphors with an interleaved 0.9 mm copper wafer. Three classes of paraffin-based nodules (0.5 to 3.0 cm) of varying mineral concentration (0, 120 and 190 mg/cm3 K2HPO4) were randomly positioned on the chest wall of two healthy volunteers to simulate calcified and non-calcified nodules. The average receiver operating characteristics (ROC) area of six readers (n = 2880 observations) showed that digital "bone" images (ROC area: 0.77 +/- 0.03) were significantly better (P less than 0.04) than conventional radiographs (OC Film, Lanex medium screens, 141 kVp, 19 mR skin exposure dose) (ROC area: 0.71 +/- 0.05) in detecting calcification in nodules. The unsubtracted digital images of lower kilovoltage were not superior to the 141 kVp conventional radiographs in a subgroup of two readers (ROC area: 0.73 +/- 0.02). Digital "soft tissue" images were equivalent to conventional chest radiographs in detecting soft tissue pulmonary nodules (ROC areas: 0.92 +/- 0.04 and 0.92 +/- 0.05, respectively.     

Massive pulmonary embolism: triple-armed therapy

Many patients who suffer a massive pulmonary embolus die despite emergent therapy. In these desperately ill patients an aggressive, combined method of management was initiated to improve their chances and quality of survival. During a 5-year period 10 patients were treated with (1) low-dose topical, intrapulmonary thrombolytic therapy to dissolve thrombus, (streptokinase or urokinase); (2) anticoagulation to prevent thrombus propagation (heparin); and (3) the simultaneous insertion of a Greenfield filter to prevent the early, recurrent, and therefore potentially fatal pulmonary embolus--"triple-armed therapy." Thrombolytic therapy was administered through a Swan-Ganz catheter wedged against the pulmonary embolus. During the same interval 10 other patients also sustained massive pulmonary emboli but were treated only with systemic heparin. Serial pulmonary arteriography was performed daily. The patients treated by triple-armed therapy responded favorably with a rapid (less than 6 hours), significant improvement in PaO2, pulmonary artery pressure, cardiac output, pulmonary vascular resistance, and blood pressure, compared with patients treated with continuous heparin alone. Nine patients in the triple-armed therapy group survived whereas only six in the heparin group survived. Two additional patients were treated by triple-armed therapy and had thrombolysis with triple-armed therapy with tissue plasminogen activator; these patients demonstrated the most rapid improvement in cardiorespiratory dynamics and arteriographic clearance of emboli. This management protocol shows promise for patients who sustain a massive pulmonary embolus, because it reduces the morbidity associated with pulmonary embolectomy while avoiding the hazards associated with systemic thrombolytic therapy.     

Renal Biopsy Pathology in Wegener''s Granulomatosis

Eighteen renal biopsies from 10 patients with active generalized Wegener's granulomatosis (GWG), with GWG in remission on therapy, and with active localized Wegener's granulomatosis (LWG) have been examined by light and electron microscopy. In all 9 patients with active GWG, light microscopy revealed focal and segmental glomerulonephritis. Electron microscopy revealed subepithelial basement membrane densities resembling immune complex deposits in two biopsies from patients with active GWG. In biopsies from patients on cytotoxic therapy, there was no active inflammatory process, but focal glomercular obsolescence and segmental tuft sclerosis provided evidence of prior focal and segmental glomercular disease. Discrete zones of basement membrane crimping and increased mesangial material along the capillary wall were observed in some patients with apparent LWG, as well as proven GWG, possibly representing foci of previous glomerular injury. The appearance of dense deposits on the epithelial side of the basement membrane suggests that immune complex deposition in the glomeruli may be at least partially responsible for the renal injury in Wegener's granulomatosis.     

A phage display system for detection of T cell receptor-antigen interactions

The process of T cell recognition involves a complex set of interactions between the various components of the TCR/MHC/peptide trimolecular complex. We have developed a system for exploring the specific binding interactions contributed by the constituent subunits of TCR complexes for components of their ligands. We utilized an M13 phage display system, designed for multivalent receptor display, to explore specific binding interactions between various TCRα chains and specific antigen in the absence of MHC. The multivalent TCR-phage display system was sensitive enough to reveal some TCRα chains capable of binding directly to antigen with the same fine specificity shown by the MHC-restricted T cells from which the α chains were derived. Cross-specificity analysis using two antigen-binding TCRα chains derived from T cells with different polypeptide antigen specificities confirmed the fidelity of this binding. In mixtures of antigen-binding and non-binding TCRα-displaying phage, specific selection was achieved at a starting frequency of 1/1000, suggesting that this system can be employed for selection and analysis of TCR-displaying phage libraries. While the binding specificities exhibited by these TCRs are unusual, they provide a novel perspective from which to study the specific binding interactions that constitute TCR antigen binding.     

Separation and Characterization of Human Neutrophil Granules

Human blood neutrophilic leukocytes were separated and purified by modifications of the Hypaque/Ficoll and dextran separation methods, resulting in a suspension which was greater than 96% neutrophils. Neutrophils were prepared in 0.34 M sucrose containing heparin and were clarified of nongranular debris by sequential passage through polycarbonate filters of pore size 5 μ and 2 μ. Isopycnic sucrose gradients of such filtrates revealed three major bands. The gradient separated fractions were studied by electron microscopy including peroxidase cytochemistry and by enzyme assay for myeloperoxidase (MPO), β-glucuronidase, muramidase alkaline phosphatase and acid phosphatase utilizing both p-nitrophenylphosphate (pnp) and β-glycerophosphate as substrates. Peroxidase-positive granules were observed at both density 1.22 (band A) and density 1.20 (band B). Three peroxidase-negative granules were identified: the round or oval peroxidase-negative granule of density 1.22 (band A) and two smaller granules, distinguishable by size and shape at density 1.18 (band C). Band C granules contain crystalloid inclusions. Peaks of muramidase activity coincided with bands A and C, suggesting the presence of muramidase in the peroxidase-negative granules of density 1.22 and in one or both of the peroxidase-negative granules at density 1.18. β-Glucuronidase was distributed like MPO, with a major peak in band B and a minor peak in band A. Acid β-glycerophosphatase was largely in band A. Acid pnp phosphatase was nonspecifically associated with soluble nongranular protein which always remained at the origin of sucrose gradients. Alkaline phosphatase was not granule associated and sedimented alone to density 1.145, which is highly suggestive of a cytoplasmic membrane localization for this enzyme.