The controversy regarding the cell of origin of white adipose tissue fat cells has not been resolved. It has not as yet been established whether a fat cell represents a modified connective tissue fibroblast which has accumulated lipid (44, 35) or is derived from a specialized perivascular reticular mesenchymal cell (174). The fat cell has been classically described as having a signet ring appearance on histological section due to the peripherally displaced flattened nucleus and the large central vacuole representing the space occupied by fat. A very thin attenuated ring of cytoplasm exists but is not readily apparent by light microscopy.

No living tissue can escape the ageing process. It may express itself by alterations in structure, function, or a combination of both. The structural alterations may be visible to the naked eye, such as greying, baldness and wrinkling of the skin. Others are more subtle and may only be seen with the microscope, such as neuronal degeneration in the cerebral cortex; and still ethers cannot be seen when examined by present methods. Examples of functional alterations that may occur with age are presbyopia, presbycusis and a fall in the lung diffusing capacity (17).

Dyspnoea is a common, if not the commonest symptom, of thyrotoxicosis (Wayne) and cardiovascular overactivity is recognized as a cardinal sign of the disease. Despite the prominence of these manifestations the underlying physiology is poorly understood. Probably the major reason for this is lack of data. Stein, et al.,(l961) have recorded a relatively comprehensive study of pulmonary function on thirteen patients at rest and on exercise. Their findings are discussed later but they, in common with all other investigators, did not report on the exercise diffusing capacity.

There has been much development in the field of respiratory physiology within the recent past, and this has been accelerated by the availability of better instruments for the purposes of making measurements. Since Hutchinson introduced the spirometer in 1846, the introduction of each new instrument has revealed a new area into which efforts of research, both clinical and purely physiological, have been directed. One of the most powerful, and yet the most simple tests of respiratory dynamic capability is the Forced Expiratory Volume, consisting of a maximal forced expiration following a maximal inspiration. It has been demonstrated that this test is a sensitive indicator of respiratory airway resistance.

From 1927 to 1930 various groups of investigators demonstrated that adrenal cortical extracts were capable of prolonging the life of adrenalectomized cats (1-4) and dogs (5). Subsequently, Wintersteiner, Vars and Pfiffner (6,7) showed that after the removal of various crystalline substances from adrenal cortical extracts, a non-crystallizable amorphous residue remained which was more active than the separated crystalline components in maintaining the life of an adrenalectomized dog. Kendall, Mason and associates (8) also found that the most physiologically active traction remained in solution and that it was at least ten times more active than compound B. similar findings were reported by Kuizenga and Cartland (9).

Anatomically the lung consists of two conducting systems to bring the inspired air and venous blood into contact. The effectiveness of gas exchange is largely dependent on the efficiency of these distribution systems. If parts of the lung are ventilated but not perfused, or perfused but not ventilated, no gas exchange will occur in these areas. Furthermore, ventilation in excess of perfusion, or perfusion in excess of ventilation are relatively inefficient. The optimum distribution is clearly when the quantities of ventilation and perfusion are matched, that is, the Ventilation/Perfusion ratio is equal in all lung units. To predict gas exchange it is therefore necessary to know not only the total quantities of alveolar ventilation and pulmonary capillary blood flow, but also their distribution.

In spite of the fact that pulmonary emphysema has been recognized for one hundred and fifty years or more, it has only been in the last fifteen years that extensive efforts have been made by anatomists, pathologists, physiologists, biochemists and clinicians to correlate its various aspects. Unfortunately these efforts have not been completely successful in clarifying the aetiology and pathogenesis of the disease and in fact until recently there was no universally accepted definition of emphysema. The definition that will be used in this study is the one proposed at the Ciba Guest Symposium (1959): “Emphysema is a condition of the lung characterized “by increase beyond the normal in the size of air spaces “distal to the terminal bronchiole either from dilatation or from destruction of their walls”.

Membrane sulfhydryl (SH) groups have been reported to be important for the maintenance of red cell integrity in vivo (Jacob and Jandl, 1962). A technique has been developed for the determination of reactive membrane sulfhydryl content in intact erythrocytes, utilizing subhemolytic concentrations of p-chloromercuribenzoate (PMB). The erythrocyte membrane of 52 healthy subjects contained 2.50 - 2.85 x 10^-16 moles of reactive SH groups (mean 2.50 +/- 0.20) per erythrocyte, when determined by this method. A 27-36% reduction of erythrocyte membrane SH content was observed in various conditions characterized by accelerated red cell destruction, including glucose- 6-phosphate dehydrogenase (G6PD) deficiency, drug-induced, autoimmune and other acquired hemolytic anemias and congenital spherocytosis. Normal membrane sulfhydryl content was found in iron deficiency anemia, pernicious anemia in relapse, and in other miscellaneous hematological conditions. Inhibition of membrane SH groups with PMB caused marked potassium leakage from the otherwise intact cells. The possible role of membrane sulfhydryl groups in the development of certain types of hemolytic anemias, and in the maintenance of active transmembrane cation transport in the erythrocyte is discussed.

While accurate measurement of the excretory aspect of renal function is clearly a vital part of the assessment and follow-up of many patients with renal or urological disease, this unfortunately is not always easy to obtain. Screening tests such as BUN, serum creatinine and I.V.P. may not become abnormal until 2/3 of renal function has been lost, so that more finite clinical tests are necessary. Those commonly used are the creatinine clearance and the P.S.P. test. It is our experience, considering the overall hospital population, that 1/4 to 1/3 of these tests give inaccurate results when the urine is collected without a catheter.

Since Liljestrand's classic work on the O2 cost of ventilation (10) there has been ample confirmation of his finding that voluntary hyperventilation requires more oxygen per litre ventilated than if hyperventilation is CO2 driven at the same frequency and tidal volume (1,6,7,10,13,17,18). Figure 1 illustrates this point graphical1y and shows two families of curves. One (solid lines), representing the oxygen cost of carbon dioxide driven hyperventilation while the other (dotted lines) represents the considerably greater oxygen cost of voluntary hyperventilation at any chosen minute ventilation. Liljestrand's explanation that the greater O2 cost of voluntary hyperventilation was due to the less efficient use of the respiratory muscles during voluntary as compared with CO2 driven hyperventilation has been generally accepted by most investigators. [...]