The use of folliculin in involutional states

In a series of 32 menopausal cases hot flashes occurred in all, paresthesias in 16, insomnia in 19, and psychotic pictures in 17. Obesity was found in only 13, and hypertension in 10. Of this series 6 had artificial climacteric produced by radiation or surgery, and there were 3 patients with a spontaneous premature menopausal picture, possibly to be considered as ovarian insufficiency.The use of simple psychotherapeutic procedures and small doses of folliculin daily or oftener has been found very helpful in the psychotic cases as well as in the simpler vasomotor types and the pseudothyrotoxic types previously reported. Disadvantages of large doses of the hormone are pointed out. The refractory nature of the artificial menopause leads to a discussion of the possible relationships of the pituitary and the ovaries at the age of the climacteric.     

THE DEACTIVATION OF RABBIT NEUTROPHILS BY CHEMOTACTIC FACTOR AND THE NATURE OF THE ACTIVATABLE ESTERASE

As shown previously, immune complexes engender in rabbit serum a factor capable of inducing chemotaxis of rabbit polymorphonuclear leukocytes. This chemotactic factor consists of a complex of the fifth, sixth, and seventh components of complement. As demonstrated here, the polymorphonuclear leukocytes incubated with such treated rabbit serum lose their ability to respond chemotactically to the chemotactic factor. They are "deactivated." The process of "deactivation" is a function of the duration of contact of the cells with, and the concentration of, the treated serum. There is a parallelism between the time course of deactivation and of chemotaxis, as well as the dose-response curves for the two processes. Chemotactic factor purified by isoelectric precipitation and ion-exchange chromatography produces deactivation in the same manner as the treated serum. The deactivating activity requires, as does the chemotactic factor, the sixth component of complement; like the chemotactic factor, it is heat-stable and nondialyzable. Deactivation is prevented by the same phosphonate esters shown previously to prevent chemotaxis by the complement-associated chemotactic factor. The profiles of the phosphonates in protecting against deactivation are the same as the profiles for the chemotactic factor-dependent inhibition of chemotaxis. Aromatic amino acid derivatives prevent both chemotaxis and deactivation. We conclude from this evidence that the chemotactic factor is able to deactivate or induce chemotaxis depending upon experimental conditions. The fact that the profiles given by the phosphonates for protection against chemotactic factor-dependent deactivation and for chemotactic factor-dependent inhibition of chemotaxis are the same indicates that the "activatable esterase" is involved in both processes. Acetate esters such as ethyl acetate and others shown previously to prevent chemotaxis by inhibiting the "activated esterase" do not prevent deactivation. This indicates that deactivation can occur without participation of the latter enzyme, implying that deactivation involves only a part of the biochemical mechanism of chemotaxis. The protection against deactivation afforded by aromatic amino acid derivatives is specific, insofar as nonaromatic amino compounds and simple acetate esters have no effect. In addition, as stated, the aromatic amino acid derivatives inhibit deactivation and chemotaxis by the chemotactic factor. This latter finding, together with the demonstration of the involvement of the activatable esterase in both deactivation and chemotaxis, suggests that the activatable esterase of the rabbit polymorphonuclear leukocyte is a serine esterase with a special affinity for aromatic amino acid derivatives.     

Orosomucoid Content of Pleural and Peritoneal Effusions

22 nonneoplastic, noninflammatory effusions (cirrhosis and congestive heart failure), 12 non-neoplastic inflammatory effusions (tuberculosis, lupus erythematosus, rheumatoid arthritis, and idiopathic pleuropericarditis), and 58 neoplastic effusions (cancer of lung, breast, ovary, and pancreas, and lymphoma) were analyzed by radial immunodiffusion for orosomucoid concentration. The average concentration +/-SE was 35+/-4, 65+/-17, and 130+/-13 mg/100 ml in the three types of effusion, respectively. By gel filtration and ion exchange chromatography, orosomucoid was isolated from 12 nonmalignant and 14 malignant fluids. The orosomucoid preparations reacted as single components in acrylamide gel electrophoresis at pH 9.0, and in immunodiffusion and immunoelectrophoresis against antisera to human serum and to human plasma orosomucoid. In radial immunodiffusion, the slope of the line relating concentration to the square of the diameter of the precipitate area was identical for orosomucoid isolated from normal human plasma and from nonneoplastic effusions, but was subnormal for orosomucoid isolated from neoplastic fluids. All orosomucoid preparations had normal amino acid composition. Orosomucoid from the nonmalignant effusions had normal carbohydrate content. 11 of 14 samples of orosomucoid isolated from neoplastic fluids had abnormalities in carbohydrate composition, consisting of subnormal content of sialic acid (11 of 14), hexose (10 of 14), and hexosamine (3 of 14), and abnormally high content of hexosamine (4 of 14).Discriminant analysis showed that concentration of orosomucoid distinguished between neoplastic and nonneoplastic noninflammatory effusions more effectively than concentration of total protein, albumin, alpha(1), alpha(2), beta, or gamma-globulin.     

Randomized trial of two mind-body interventions for weight-loss maintenance

OBJECTIVE: Regain of weight after initial weight loss constitutes a major factor contributing to the escalating obesity epidemic. The objective of this study was to determine the feasibility and clinical impact of two mind-body interventions for weight-loss maintenance. DESIGN: Randomized, balanced, controlled trial. SETTING: Large-group model health maintenance organization. PARTICIPANTS: Overweight and obese adults were recruited to a 12-week behavioral weight-loss program. Participants meeting threshold weight loss and attendance requirements were eligible for randomization. INTERVENTIONS: The three weight-loss maintenance interventions were qigong (QI), Tapas Acupressure Technique (TAT (registered trademark of Tapas Fleming, L.Ac.), and a self-directed support (SDS) group as an attention control. OUTCOMES: The main outcome measure was weight loss maintenance at 24 weeks postrandomization. Patient interviews explored additional benefits of the interventions, as well as barriers and facilitators to compliance. RESULTS: Eighty-eight percent (88%) of randomized patients completed the study. There were no significant study-related adverse events. At 24 weeks, the TAT group maintained 1.2 kg more weight loss than the SDS group did (p = 0.09), and 2.8 kg more weight loss than the QI group did (p = 0.00), only regaining 0.1 kg. A separation test (0.05 level, 0.95 power) indicated that TAT merits further study. A secondary analysis revealed that participants reporting a previous history of recurrent unsuccessful weight loss were more likely to regain weight if assigned to the SDS arm, but this effect was suppressed in both the QI and TAT groups (p = 0.03). Although QI participants reported important general health benefits, the instruction sequence was too brief, given the complexity of the intervention. CONCLUSIONS: TAT warrants further research for weight-loss maintenance. Any further research on qigong should use a modification of our protocol.     

Group-Based Trajectory Modeling of Suppression Ratio After Cardiac Arrest

Background

Existing studies of quantitative electroencephalography (qEEG) as a prognostic tool after cardiac arrest (CA) use methods that ignore the longitudinal pattern of qEEG data, resulting in significant information loss and precluding analysis of clinically important temporal trends. We tested the utility of group-based trajectory modeling (GBTM) for qEEG classification, focusing on the specific example of suppression ratio (SR).

Methods

We included comatose CA patients hospitalized from April 2010 to October 2014, excluding CA from trauma or neurological catastrophe. We used Persyst^®v12 to generate SR trends and used semi-quantitative methods to choose appropriate sampling and averaging strategies. We used GBTM to partition SR data into different trajectories and regression associate trajectories with outcome. We derived a multivariate logistic model using clinical variables without qEEG to predict survival, then added trajectories and/or non-longitudinal SR estimates, and assessed changes in model performance.

Results

Overall, 289 CA patients had ≥36 h of EEG yielding 10,404 h of data (mean age 57 years, 81 % arrested out-of-hospital, 33 % shockable rhythms, 31 % overall survival, 17 % discharged to home or acute rehabilitation). We identified 4 distinct SR trajectories associated with survival (62, 26, 12, and 0 %, P < 0.0001 across groups) and CPC (35, 10, 4, and 0 %, P < 0.0001 across groups). Adding trajectories significantly improved model performance compared to adding non-longitudinal data.

Conclusions

Longitudinal analysis of continuous qEEG data using GBTM provides more predictive information than analysis of qEEG at single time-points after CA.

     

MECHANISMS OF IMMUNOLOGIC INJURY OF RAT PERITONEAL MAST CELLS : I. THE EFFECT OF PHOSPHONATE INHIBITORS ON THE HOMOCYTOTROPIC ANTIBODY-MEDIATED HISTAMINE RELEASE AND THE FIRST COMPONENT OF RAT COMPLEMENT

The ability of a number of p-nitrophenylethyl, alkyl phenylalkyl, chloroalkyl, and aminoalkyl phosphonates to inhibit the homocytotropic antibody-mediated release of histamine from rat peritoneal mast cells has been tested. The effectiveness of these same phosphonates against the activated first component of rat complement (C'1a) has also been investigated. The rat mast cell esterase activated by the reaction of antigen and homocytotropic antibody resembles chymotrypsin in its reactivity with the phenylalkyl and chloroalkyl phosphonate, but is unlike this protease in its greater responsiveness to the 5-aminopentyl phosphonate relative to the pentyl phosphonate. The antigen-homocytotropic antibody-activated mast cell esterase and chymotrypsin, thus, appear to be similar, but different enzymes; i.e., they are parazymes (see reference 4, p. 501). There are distinct differences in the pattern of inhibition given by the phenylalkyl and aminoalkyl and alkyl phosphonates of the homocytotropic antibody-mediated histamine release from rat peritoneal mast cells and from guinea pig lung slices. On the basis of these differences it is concluded that the esterases activated by the combination of antigen and homocytotropic antibody on the mast cells of the two species are not the same. The arithmetic dose response curve found for the action of the phosphonates on the antigen-induced histamine release from rat peritoneal mast cells contrasted sharply with the logarithmic relationship found when these same inhibitors acted on the guinea pig lung system. This suggests that in addition to the antigen-antibody-activated esterases being unlike, the detailed mode of histamine release from the mast cells of the guinea pig lung differs from that of the mast cells of the rat peritoneum. Distinct and large differences were found in the pattern of inhibition of histamine release from rat peritoneal mast cells and of rat C'1a given by the phenylalkyl, and chloroalkyl and alkyl phosphonates implying that esterase activated by the combination of antigen with the sensitized rat peritoneal mast cells is not C'1a. Thus, the results with the peritoneal mast cells lead to the same conclusion as the previous work with guinea pig lung slices; i.e., the antigen-antibody-activated esterase involved in the homocytotropic antibody-mediated release of histamine is not part of the complement system.     

Microbiologic follow-up study in adult bronchiectasis

There is minimal published longitudinal data about pathogenic microorganisms in adults with bronchiectasis. Therefore a study was undertaken to assess the microbiologic profile over time in bronchiectasis. A prospective study of clinical and microbiologic outcomes was performed. Subjects were assessed by a respiratory physician and sputum sample were collected for analysis. Subjects were followed up and had repeat assessment performed. Eighty-nine subjects were followed up for a period of 5.7+/-3.6 years. On initial assessment the two most common pathogens isolated were Haemophilus influenzae (47%) and Pseudomonas aeruginosa (12%) whilst 21% had no pathogens isolated. On follow-up review results were similar (40% H. influenzae, 18% P. aeruginosa and 26% no pathogens). The prevalence of antibiotic resistance of isolates increased from 13% to 30%. Analysis of a series of H. influenzae isolates showed they were nearly all nontypeable and all were different subtypes. Subjects with no pathogens isolated from their sputum had the mildest disease, while subjects with P. aeruginosa had the most severe bronchiectasis. Many subjects with bronchiectasis are colonized with the same bacterium over an average follow-up of 5 years. Different pathogens are associated with different patterns of clinical disease.