Improved exercise tolerance after losartan and enalapril in heart failure: correlation with changes in skeletal muscle myosin heavy chain composition

BACKGROUND: In congestive heart failure, fatigue-resistant, oxidative, slow type I fibers are decreased in leg skeletal muscle, contributing to exercise capacity (EC) limitation. The mechanisms by which ACE inhibitors and AII antagonists improve EC is still unclear. We tested the hypothesis that improvement in EC is related to changes in skeletal muscle composition toward type I fibers. METHODS AND RESULTS: Eight patients with congestive heart failure, NYHA classes I through IV, were treated for 6 months with enalapril (E) 20 mg/d, and another 8 with losartan (L) 50 mg/d. EC was assessed with maximal cardiopulmonary exercise testing at baseline and after treatment. Myosin heavy chain (MHC) composition of the gastrocnemius was studied after electrophoretic separation of slow MHC1, fast oxidative MHC2a, and fast glycolytic MHC2b isoforms from needle microbiopsies obtained at baseline and after 6 months. EC improved in both groups. Peak V(O2) increased from 21.0+/-4.7 to 27.6+/-4.3 mL . kg-1 . min -1 (P=0.011) in the L group and from 17.5+/-5.0 to 25.0+/-5.5 mL . kg-1 . min -1 (P=0.014) in the E group. Similarly, ventilatory threshold changed from 15.0+/-4.0 to 19.9+/-4.9 mL (P=0. 049) with L and from 12.0+/-1.9 to 15.4+/-3.5 mL (P=0.039) with E. MCH1 increased from 61.2+/-11.2% to 75.4+/-7.6% with L (P=0.012) and from 60.6+/-13.1% to 80.1+/-10.9% (P=0.006) with E. Similarly, MHC2a decreased from 21.20+/-9.5% to 12.9+/-4.4% (P=0.05) with L and from 19.9+/-7.8% to 11.8+/-7.9% (P=0.06) with E. MHC2b changed from 17. 5+/-6.5% to 11.7+/-5.2% (P=0.07) with L and from 19.5+/-6.4% to 8. 1+/-4.6% (P=0.0015) with E. There was a significant correlation between net changes in MHC1 and absolute changes in peak V(O2) (r2=0.29, P=0.029) and a trend to significance for MHC2a and 2b. CONCLUSIONS: Six months' treatment with L and with E produces an improvement in EC of similar magnitude. These changes are accompanied by a reshift of MHCs of leg skeletal muscle toward the slow, more fatigue-resistant isoforms. Magnitude of MHC1 changes correlates with the net peak V(O2) gain, which suggests that improved EC may be caused by favorable biochemical changes occurring in the skeletal muscle.     

Breathing at low lung volumes and chest strapping: a comparison of lung mechanics

In six normal subjects forced expiratory flow rates increased progressively with increasing degrees of chest strapping. In nine normal subjects forced expiratory flow rates increased with the time spent breathing with expiratory reserve volume 0.5 liters above residual volume, the increase being significant by 30 s (P less than 0.01), and flow rates were still increasing at 2 min, the longest time the subjects could breathe at this lung volume. The increase in flow after low lung volume breathing (LLVB) was similar to that produced by strapping. The effect of LLVB was diminished by the inhalation of the atropinelike drug ipratropium. Quasistatic recoil pressures were higher following strapping and LLVB than on partial or maximal expiration, but the rise in recoil pressure was insufficient to account for all the observed increased in maximum flow. We suggest that the effects of chest strapping are due to LLVB and that both cause bronchodilatation.     

Diagnosis of adnexal malignancies by using color Doppler energy imaging as a secondary test in persistent masses

In this study we evaluated the histomorphology and ultrastructure of the oviduct of newly hatched chicks, as well as the immunohistochemical expression of progesterone receptor (PR) in this tissue after follicle-stimulating hormone (FSH) treatment on days 13, 15 and 17 of embryonic development. Results indicated a marked difference in the histology of the oviduct of newly hatched chicks treated with FSH. Magnum mucosa from these animals presented a pseudostratified epithelium with evaginations from the lumen into the epithelium and from the latter into the stroma beneath where tubular glands are formed. In contrast magnum mucosa from control animals presented columnar epithelium with no evaginations. In magnum epithelium FSH also induced the formation of cilia and microvilli projections into the lumen as well as an increase in the wall and lumen areas and in the density of nuclei per unitarea. PR immunoreactivity was only observed in the oviduct of FSH treated animals. PR was located in the nucleus of epithelial luminal cells, mucosal stromal cells and smooth muscle cells. These findings suggest that FSH induces an adequate hormonal milieu for the cytodifferentiation and PR gene expression in the chick oviduct.     

Comparison of hemoglobin A1C results by two different methods on patients with structural hemoglobin variants

OBJECTIVES: The objective was to compare hemoglobin A1C (HbA1C) results obtained by two methods based on different analytical principles for individuals with a structural hemoglobin variant. DESIGN AND METHODS: Hemoglobin A1C results were obtained using the Bio-Rad Variant (based on cation exchange chromatography) and the Bayer DCA 2000 (based on an immunological reaction) on individuals with a structural hemoglobin variant. The identity of the hemoglobin variant was confirmed by high pressure liquid chromatography (HPLC) and electrophoresis. RESULTS: Hemoglobin A1C results obtained by the two methods on individuals with S, C, D, and E trait were in close agreement. CONCLUSION: The Bio-Rad Variant and Bayer DCA 2000 produce equivalent hemoglobin A1C results on patients with S, C, and E trait. With appropriate correction, correlation of hemoglobin A1C results from the Bio-Rad Variant for individuals with D trait was good (r = 0.927). Glycohemoglobin results obtained by the two methods for some unusual structural hemoglobin variants were in close agreement.     

Expression of human lysozyme mRNA in the mammary gland of transgenic mice

Owing to its inherent antimicrobial effect and positive charge, the expression of human lysozyme in bovine milk could be beneficial by altering the overall microbial level and the functional and physical properties of the milk. We have used transgenic mice as model systems to evaluate the expression of human lysozyme containing fusion gene constructs in the mammary gland. Expression of human lysozyme was targeted to the mammary gland by using the 5' promoter elements of either the bovine beta (line B mice) or alpha s1 (line H mice) casein genes coupled to the cDNA for human lysozyme. Expression of human lysozyme mRNA was not found in mammary tissue from any of line B mice. Tissues were analysed from six lines of H mice and two, H6 and H5, were found to express human lysozyme mRNA in the mammary gland at 42% and 116%, respectively, of the levels of the endogenous mouse whey acidic protein gene. At peak lactation, female mice homozygous for the H5 and H6 transgene have approximately twice the amount of mRNA encoding human lysozyme as hemizygous animals. Expression levels of human lysozyme mRNA in the mammary gland at time points representing late pregnancy, early, peak and late lactation corresponded to the profile of casein gene expression. Human lysozyme mRNA expression was not observed in transgenic males, virgin females or in the kidney, liver, spleen or brain of lactating females. A very low level of expression of human lysozyme mRNA was observed in the salivary gland of line H5.     

Occurrence and clinical correlates of psychiatric comorbidity in patients with psychotic disorders

BACKGROUND: The aim of this study was to explore patterns and clinical correlates of psychiatric comorbidity in patients with schizophrenia spectrum disorders and mood spectrum disorders with psychotic features. METHOD: Ninety-six consecutively hospitalized patients with current psychotic symptoms were recruited and included in this study. Index episode psychotic diagnosis and psychiatric comorbidity were assessed using the Structured Clinical Interview for DSM-III-R-Patient Version (SCID-P). Psychopathology was assessed by the SCID-P, Brief Psychiatric Rating Scale, Scale for the Assessment of Negative Symptoms, and Hopkins Symptom Checklist. Awareness of illness was assessed with the Scale to Assess Unawareness of Mental Disorders. RESULTS: The total lifetime prevalence of psychiatric comorbidity in the entire cohort was 57.3% (58.1% in schizophrenia spectrum disorders and 56.9% in mood spectrum psychoses). Overall, panic disorder (24%), obsessive-compulsive disorder (24%), social phobia (17.7%), substance abuse (11.5%), alcohol abuse (10.4%), and simple phobia (7.3%) were the most frequent comorbidities. Within the group of mood spectrum disorders, negative symptoms were found to be more frequent among patients with psychiatric comorbidity than among those without comorbidity, while such a difference was not detected within the group of schizophrenia spectrum disorders. Social phobia, substance abuse disorder, and panic disorder comorbidity showed the greatest association with psychotic features. An association between earlier age at first hospitalization and comorbidity was found only in patients with unipolar psychotic depression. Patient self-reported psychopathology was more severe in schizophrenia spectrum patients with comorbidity than in those without, while such a difference was less pronounced in mood spectrum psychoses. CONCLUSION: These findings suggest that psychiatric comorbidity is a relevant phenomenon in psychoses and is likely to negatively affect the phenomenology of psychotic illness. Further studies in larger psychotic populations are needed to gain more insight into the clinical and therapeutic implications of psychiatric comorbidity in psychoses.