Left heart function in chronic obstructive lung disease

Summary In patients with varying degrees of chronic obstructive pulmonary disease (COPD), simultaneous measurements of central hemodynamics and left ventricular radionuclide ventriculograms at rest and during exercise were made. In 21 of these patients, satisfactory echocardiograms could be performed. In seven of the patients, arterial blood pressure at rest was increased. Decreased compliance of the left ventricle was thought to be present in patients with COPD and additional arterial hypertension. The left ventricular ejection fraction (LVEF) at rest was in the high normal range in all patients. During exercise, no further increase was observed. This pattern of LVEF response seems to be typical in patients with COPD. Because the highest values were observed in the more severe COPD and right ventricular hypertrophy, it is unlikely that an impairment of left ventricular function is caused by COPD. In five of 27 patients, an abnormal decrease of LVEF and regional hypokinesis occurred during exercise, thus suggesting additional coronary heart disease. The fact that at least 30% of the patients with COPD suffered from arterial hypertension and 20% of the patients exhibited unexpected ischemia detected by regional hypokinesis in RNV during exercise, but not in the ECG, may be of practical relevance. Coronary angiography was not indicated because most of these patients were over 65 and the factor limiting the working capacity was ventilatory impairment and not angina pectoris, in all patients. For this reason, a diagnostic uncertainty remains with regard to additional coronary heart disease in the older patients with advanced chronic obstructive pulmonary disease.Lung Function Parameters VC (1) inspiratory vital capacity - FEV1 (1) forced exspiratory volume in 1 sec - Raw (cmH20/l/s) airways resistance - RV/TLC (%) residual volume/total lung capacity - paO₂ (mm Hg) O₂ partial pressure Hemodynamic Parameters CI (1/min/sqm) cardiac index - SVI (ml/sqm) stroke volume index - PAP (mm Hg) pulmonary artery mean pressure - PwP (mm Hg) pulmonary capillary wedge pressure - RRs (mm Hg) systolic arterial pressure - RRd (mm Hg) diastolic arterial pressure (at the time of catheterization) - RR(WHO) (mm Hg) mean values measured at different days (at least 3 values). Parameters Derived from Combined Radionuclide Ventriculography and Central Hemodynamics LVEF (%) left ventricular ejection fraction - LVESVI (ml/sqm) left ventricular endsystolic volume index - P/V (mm Hg/ml/sqm) peak systolic pressure/endsystolic volume index - PFR (1/sec) peak filling rate: endsystolic volume/sec Echocardiographic Parameters RV d wth (mm) right ventricular enddiastolic wall thickness - LV d wth (mm) left ventricular enddiastolic wall thickness In honor to Prof. W.E. Adam's 60th birthday     

Right ventricular function in patients with chronic obstructive pulmonary disease

Summary Simultaneous right heart catheterization and radionuclide ventriculography were performed in 27 patients with a wide range of chronic obstructive pulmonary disease. Central hemodynamics and radionuclide studies were done at rest and during exercise. In the resting state the right ventricular ejection fraction (RVEF) was in the normal range (43.3±6%). During exercise a significant (p<0.001) decrease of RVEF to 38.8±6.7% occurred. The pumonary artery mean pressures were 19.9±3.8 at rest. During exercise a significant (p<0.001) increase to 41±9.8 mm Hg occurred. There was a linear relationship between pulmonary pressures and RVEF during exercise in patients with pulmonary artery pressures not exceeding 35 mm Hg. In patients with right ventricular end-diastolic wall thickness 6 mm a curvilinear relationship between these parameters could be observed with a flattening of the curve at higher pressures (>35 mm Hg) and lower ejection fractions (<35% RVEF). Radionuclide venticulography cannot substitute for right heart catheterization. Echocardiography is useful for interpretation of right ventricular ejection fractions in advanced chronic obstructive pulmonary disease.Abbreviations CI Cardiac index (l/min/m²) - CO Cardiac output (l/min) - COPD Chronic obstructive pulmonary disease - FEV₁ Forced expiratory volume in the first second (ml) - HR Heart rate (B/min) - PAd Pulmonary artery diastolic pressure (mm Hg) - PAP Pulmonary artery mean pressure (mm Hg) - PAs Pulmonary artery peak pressure (mm Hg) - PVR Pulmonary vascular resistance (dyn·s·cm^–5) - PwP Pulmonary capillary wedge pressure (mm Hg) - RAP Right arterial pressure (mm Hg) - Raw Airway resistance (cm H₂/l/s) - RNV Radionuclide ventriculogram - RV Residual volume (l) - RVEF Right ventricular ejection fraction (%) - RVEDVI Right ventricular enddiastolic volume index (ml/m²) - RVEDVI SVI RVEF (ml/m²) - RVESVI Right ventricular endsystolic index (m²/m²) - SVI Stroke volume index (ml/m²) - TLC Total lung capacity (l) - VC Vital capacity (l)     

Gastrin-releasing peptide, a mammalian analog of bombesin, is present in human neuroendocrine lung tumors.

Several reports have indicated that the amphibian peptide bombesin is present in oat-cell carcinoma of the human lung. The recent observation that gastrin-releasing peptide (GRP), a 27-amino acid peptide isolated from porcine intestine, may be the mammalian analog of bombesin led the authors to look for this peptide in human pulmonary tumors. Examination of 36 human lung tumors (8 carcinoids, 8 oat-cell carcinomas, and 20 non-oat-cell carcinomas) by immunohistochemistry and radioimmunoassay demonstrated the presence of high, although variable, levels of GRP in neuroendocrine tumors, and not in other histologic types. These findings indicate that bombesin immunoreactivity in human lung tumors should be attributed to GRP or GRP-like molecules and that GRP may be a useful marker of neuroendocrine differentiation.     

The role of relative osteoneural growth in the gross morphogenesis of the skeleton: A hypothesis

Summary A unifying concept of gross skeletal (neurocranial, neurospinal and appendicular) morphogenesis is proposed. It is based on a close developmental relationship of bone and the nervous tissue, most evident in the neurocranium. The neurospinal developmental interrelationship is modified by the neurovertebral growth differential, which appears to influence the development of spinal curvatures and the gross morphological features of the individual vertebrae. Disproportion in osteoneural growth, as a general biological phenomenon, would be expected to affect the development of the appendicular skeleton. The gross shape of the long bones (physiological curvature and epimetaphyseal widening/modelling) appear to result from a buildup of rapidly forming skeletogenic material adjacent to slower growing nervous trunks, as is the case with the enchondrally developing vertebral body.Pathological accentuation of vertebro-osteoneural growth disproportion, brought about mainly by inhibition of the vulnerable neural growth, will result in abnormal gross features of the skeleton, i.e., pathological curvatures, terminal or general thickening and shortening of bones, or dislocation of joints. Experimental and clinical deformities, such as idiopathic scoliosis, achondroplastic conditions, congenital dislocation of the hip joint, and some other bone dysplasias confined in their onset and progression to the growth period of life, seem to be related to the suggested mechanism. For the above-mentioned skeletal disorders the term osteoneural growth pathology is proposed.

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Le rôle de la croissance relative ostéo-neurale dans la morphogénèse du squelette. Une hypothèse

Résumé On propose une conception unitaire de la morphogénèse normale et pathologique du squelette axial et appendiculaire, à partir des relations les plus étroites existant entre la croissance des systèmes osseux et nerveux; la région neurocraniale en est la manifestation la plus expressive. La disproportion de croissance neuro-vertébrale en longueur exerce une influence décisive sur l'installation des courbures vértébrales physiologiques et sur les caractères morphologiques de chacune des vertèbres, aussi bien dans les dimensions des corps vértébraux que la forme du trou vertébral et des trous de conjugaison. Evoquant un phénomène biologique général, la disproportion de croissance ostéo-neurale agit de même sur le développement du squelette des membres. La forme, c'est-à-dire leurs courbures physiologiques et le modelage de la région épi-métaphysaire peuvent aussi être rattachés à un phénomène d'amassement de tissus osseux proliférant plus rapidement le long des troncs nerveux périphériques.L'accentuation pathologique de la disproportion de croissance ostéo-neurale, du fait principalement de l'inhibition de la croissance des structures nerveuses peut aboutir à des modifications des parties correspondantes du squelette avec effets de raccourcissement, de courbures pathologiques, d'élargissement partiel ou total et éventuellement, de dislocation articulaire. La conception proposée s'appuie sur des observations expérimentales de croissance ostéo-neurale chez des embryons d'oiseaux et d'amphibiens. On peut expliquer certaines déformations du squelette expérimentales ou cliniques comme la scoliose idiopathique, l'achondroplasie et la dysplasie congénitale de hanche par un même mécanisme d'adaptation des os en croissance à des troubles du développement des structures nerveuses avoisinantes. Une dénomination commune est proposée pour ces troubles de la croissance: pathologie de la croissance relative ostéo-neurale.

     

Elektronenmikroskopische Befunde an inneren Organen bei Morbus Fabry

Zusammenfassung Es werden elektronenmikroskopische Beobachtungen zur Lokalisation und zur Feinstruktur der Glykolipideinschlüsse in verschiedenen inneren Organen bei Morbus Fabry berichtet. Die intrazellulÄren und extrazellulÄren Einschlüsse bestehen aus vielschichtig lamellÄren Membransystemen in konzentrischer und exzentrischer sowie in stapeiförmiger paralleler Anordnung. Diese lamellÄre Anordnung ist charakteristisch für flüssigkristalline Phasen von Phospholipid-Wasser-Systemen. Erstmalig werden ultrastrukturelle Befunde an den inneren Organen einer erkrankten Frau mitgeteilt. Demzufolge lassen sich bei heterozygoten Frauen gleiche Glykolipidablagerungen wie bei homozygoten MÄnnern nachweisen. Die Beziehung der Glykolipideinschlüsse zu den Lysosomen wird erörtert.

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Electron microscopic observations in internal organs in morbus fabry

Summary Electron microscopic findings are reported on the localization and fine structure of glycolipid inclusions in different organs (heart, kidney, lymph nodes, arterial blood vessels, pancreas) in Fabry's disease in a female. The intracellular and extracellular inclusions were made up of multilamellar membraneous systems in concentric, excentric, and parallel arrangement. This fine structure is characteristic of liquid-crystalline phases of phospholipid-water systems.The same type of inclusions are found in the internal organs of heterozygotic women as in homozygotic men. The relationship between the glycolipid inclusions and the lysosomes is discussed.

Herrn Prof. Dr. F. Bolck, Direktor des Pathologischen Instituts der Friedrich-Schiller-UniversitÄt Jena, zum 60. Geburtstag gewidmet.     

Bromsulfalein-Kinetik mit albumingebundenem BSP

Zusammenfassung Die Beeinflussung der BSP-Kinetik durch Zusätze von Albumin zur Injektionslösung wurde geprüft. Bei einer Dosierung von 5 mg BSP pro kg Körpergewicht bleibt die Eliminationshalbwertzeit bis zu einem BSP-Albuminverhältnis von 1:10 (w/w) unverändert, nach größeren Albumingaben ist sie signifikant verlängert.F.H. Dost zum 65. Geburtstag zugeeignet     

Effect of synthetic lipopeptides formulated in liposomes on the maturation of human dendritic cells

Diacylated (e.g. MALP-2) and triacylated (Pam(3)Cys derivatives) lipopeptides, deriving from the N-terminal moiety of respectively mycoplasmal and E. coli lipoproteins, are powerful adjuvants recognized by Toll-like receptors (TLR) which have been used successfully to trigger cell activation and immune responses. To design liposome-based vaccination constructs in which Th and CTL epitopes are conjugated to synthetic lipopeptide analogues anchored into the bilayers of the vesicles, the peptide moieties of the lipopeptides were functionalized with thiol-reactive groups, such as maleimide (Mal) or bromoacetyl, incorporated into liposomes and reacted with thiol carrying peptide epitopes. Because dendritic cells (DCs) play a key role as antigen-presenting cells in immune responses, in the present study we have evaluated the impact of the functionalization of lipopeptide analogues Pam(2)CAG, Pam(3)CAG and Ol(3)GAG on the phenotypic maturation of human monocyte-derived DCs. The intrinsic cellular activities of the lipopeptide analogues incorporated into liposomes were monitored, in vitro, by measuring the up-regulation of the cell-surface markers CD80, CD83, CD86 and HLA-DR. We found that in some cases their functionalization with thiol-reactive groups led to a loss of activity. The stimulatory potency can be ranked in the following order: Pam(3)CAG>/=Pam(2)CAG-Mal-Th approximately Pam(2)CAG-Mal>Pam(3)CAG-Mal-Th (where Th is a HS-peptide) and no appreciable activity was detected for Pam(3)CAG-Mal, Ol(3)CAG-Mal and Ol(3)CAG-Mal-Th. Our findings indicate that subtle modifications in the peptide moiety of lipopeptides have a great impact on the immunomodulatory properties of these molecules. For the engineering of liposome/lipopeptide-based vaccines, the maleimide derivative of Pam(2)CAG appears to be the best candidate.     

Epiphyseal dysplasia of the femoral head, mild vertebral abnormality, myopia, and sensorineural deafness: report of a pedigree with autosomal dominant inheritance.

A family is presented with short stature, femoral epiphyseal dysplasia, mild vertebral changes, and sensorineural deafness inherited as an autosomal dominant trait. Myopia and retinal detachment presenting in adult life were also present in some affected members. We suggest that this disorder may be a distinct entity within the spondyloepiphyseal dysplasia group of disorders.