Lung mechanics--the inverse problem.

The mechanical properties of the lung are important determinants of its efficacy as a gas exchanging organ. These properties are reflected to a precise degree in the relationships between pressure and flow measured at the mouth. Together with oesophageal pressure, which reflects the pressure in the pleural space, these quantities allow one to usefully indulge in inverse modelling of the lung - that is, identify mathematical models of lung mechanics that give insight into its structure and may be diagnostic of certain diseases. The complexity of such models, however, is limited by the number of distinct components that can be unambiguously resolved from the measured signals. The development of more detailed models requires the availability of experimental methods for obtaining additional input-output information from the lungs. One such method is the so-called alveolar capsule technique which allows alveolar pressures at several sites on the lung surface to be measured directly. This technique has been used in animals to show that the mechanical behaviour of normal lungs in the breathing frequency range is well described by a homogeneously ventilated compartment surrounded by viscoelastic tissue. During bronchoconstriction, however, the lungs can become markedly inhomogeneous resulting from differences in regional resistive and elastic properties. Model ambiguity problems again appear as it becomes impossible to distinguish changes in local resistance from changes in elastance using only the information obtained from alveolar capsules. To push the inverse modelling of the lung one step further, we have recently developed a new technique for quantifying changes in local resistance and elastance by applying broad-band oscillations in flow to the lung through a small hole in the pleura, thereby obtaining an alveolar input impedance.     

The management of preexcitation syndromes

The introduction of new techniques such as epicardial mapping and programmed stimulation of the heart has made it possible to unravel most of the mysteries surrounding ventricular preexcitation. They helped us to understand the mechanisms of the arrhythmias that frequently are found in these patients and led to better-directed therapeutic interventions. The purpose of this article is to review this information and to indicate how it can be used in the treatment of the patient with preexcitation.     

A three-year prospective study of systemic manifestation in rheumatoid arthritis

Clinical Rheumatology - Rheumatoid arthritis (RA) as a systemic disease can attack many other organs in addition to the joints. A variety of pathological lesions of the blood vessels are...     

Functional renal insufficiency during long-term therapy with captopril and enalapril in severe chronic heart failure

Renal function was evaluated in 104 patients with severe chronic heart failure whom we treated with captopril or enalapril. Seventy patients showed no change or an improvement in renal function (group A), and 34 patients developed functional renal insufficiency (group B). Before converting-enzyme inhibition, group B patients received higher doses of furosemide (p less than 0.02) and had lower central venous pressures (p less than 0.05) than group A patients. After 1 to 3 months of converting-enzyme inhibition, an excessive reduction in left ventricular filling pressure (to less than 15 mm Hg) or mean arterial pressure (to less than 60 mm Hg) was noted in 28 of 34 (82%) patients in group B but in only 22 of 70 patients in group A (31%) (p less than 0.001). At the end of the study, drug-induced azotemia resolved after a reduction in the dosage of diuretics, despite unaltered treatment with captopril and enalapril. Hence, the deterioration of renal function after converting-enzyme inhibition in heart failure is not a toxic or immunologic reaction to therapy but results from specific hemodynamic events that can be ameliorated by sodium repletion.     

Plasma levels of amino acids correlate with motor fluctuations in parkinsonism

Seven patients with Parkinson's disease who experienced severe motor fluctuations in response to levodopa were studied in detail with relation to the effect of dietary protein on their motor function. The levodopa dose for each patient was not changed during the period of study, and no other antiparkinsonian drugs were used. Regular and high-protein diets resulted in a marked elevation in the plasma concentrations of large neutral amino acids (LNAAs) that are known to compete with levodopa for transport across the blood-brain barrier. Despite elevated plasma levodopa levels, all patients with elevated LNAA levels experienced parkinsonian symptoms. When the amino acid level dropped while plasma levodopa levels were elevated, patients experienced relief of these symptoms. On a low-protein diet, LNAA levels remained low and all patients were consistently dyskinetic throughout the day, even though the mean plasma levodopa levels were somewhat lower than when the patients consumed a high-protein diet. A redistribution diet that is virtually protein free until supper and then unrestricted until bedtime is tolerated by patients because this simple manipulation permits near-normal daytime motor function.     

Acute effects of nitroglycerin on the energetics of the human left ventricular myocardium

We analyzed performance and efficiency of the left ventricular myocardium on the basis of two new energetic parameters. The myocardial energy consumed during one cardiac cycle is related to performed work on the one hand (E1) and to the stress-time-integral on the other (E2). E1 was obtained by analysis of the pressure-volume integral divided by left ventricular muscle mass. E2 was obtained as follows: the stress-time integral was analyzed from pressure-volume data and wall thickness using an ellipsoidal calculation model. In order to transfer the stress-time integral into energy units, the value was multiplied by a constant factor which was obtained in experimental myothermal studies. In ten patients with coronary heart disease undergoing diagnostic heart catheterization, angiocardiography was performed before and after oral administration of nitroglycerin (1.6 mg). Total energy consumption (2E1 + E2) per gram myocardium per beat decreased from 6.1 +/- 1.3 mcal/g to 4.7 +/- 1.4 mcal/g (P less than 0.01), and myocardial efficiency (E1/[2E1 + E2]) increased from 27.0 +/- 3.1% to 28.4 +/- 4.3% (N.S.) on the average. This analysis explains quantitatively the beneficial effect of nitro-preparations on myocardial function and energetics.     

Changes of lens crystallins photosensitized with tryptophan metabolites

The effect of UV irradiation on bovine lens soluble proteins (crystallins) in the presence of tryptophan metabolites was investigated in vitro. The cross-linking of crystallins by UV irradiation was accelerated by kynurenine, 3-hydroxykynurenine, anthranilic acid and 3-hydroxyanthranilic acid. On denaturation of crystallins by photooxidation, alpha-crystallin was characterized by the formation of water-soluble HMW (high molecular weight) protein, while water-insoluble HMW protein was produced from beta- and gamma-crystallin. These HMW aggregates showed cross-linking by non-disulfide covalent bonds. LMW (low molecular weight) peptides were formed by degradation of alpha- and beta-crystallin.