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The beta 2-receptor agonist class of drugs is metabolized in humans almost exclusively by sulfate conjugation. The objective of this investigation was to determine the influence of chemical structure on the stereoselectivity of the sulfoconjugation of these chiral drugs. The pure enantiomers of six beta 2-agonists, including those clinically most widely used, were all effectively sulfated both by the cytosol of the human intestine and the recombinant human M-form phenolsulfotransferase (PST). Whereas the apparent Km values (Km,app) for the sulfation of the individual drug enantiomers by the intestinal cytosol varied widely, ranging from 4.8 microM for (S)-isoproterenol to 889 microM for (S)-albuterol, these Km,app values were highly correlated with those obtained with M-PST (correlation coefficient 0.994). In contrast, the M-PST Vmax,app values were similar for all drug enantiomers, ranging from 276 to 914 pmol min-1 mg-1 protein, implying that substrate binding to M-PST by far is the main determinant of the sulfation activity. For isoproterenol, the Km,app for M-PST was 6.1 times higher for the active (R)- than for the inactive (S)-enantiomer. For other beta 2-agonists, the stereoselectivity decreased towards unity as the Km,app increased. However, for albuterol, containing a hydroxymethyl substituent at the aromatic ring, the stereoselectivity was dramatically reversed, with 10 times higher Km,app for the inactive (S)- than for the active (R)-enantiomer.

1 The metabolism of (+)-, (-)- and (±)-salbutamol by sulphoconjugation was determined in vitro using human lung cytosol and bronchial epithelial BEAS-2B cell homogenate. 2 For the lungs the intrinsic clearance (Vmax/Km) value for the pharmacologically active (-)-salbutamol (0.49 ± 0.32 ml min--1 g-1 protein) exceeded that of (+)-salbutamol (0.046 ± 0.028 ml min-1 g-1 protein) by 11-fold. This was mainly due to a difference in Km value, which was 16 times higher for (+)-salbutamol (1300 ± 170 μM) than for (-)-salbutamol (83 ± 12 μM). 3 The stereoselectivity of sulphoconjugation of salbutamol was very similar in the BEAS-2B cells, although the absolute activity was considerably lower. 4 The enzyme catalyzing this reaction both in the lungs and in the BEAS-2B cells was the monoamine (M) form phenolsulphotransferase. 5 These observations emphasize that the smooth muscle of the bronchi most likely are exposed to considerably higher concentrations of the potentially toxic (+)-enantiomer than of the bronchodilating (-)-enantiomer during therapy with (±)-salbutamol.

IN 1930 Cushing (I) described a peculiar syndrome associated with basophilic tU-mors of the pituitary. This syndrome is characterized by obesity confined to the face and trunk, redness of the face, cyanotic striae distensae over the trunk, ec-chymoses on the lower extremities, and acneiform eruptions. In females there is also amenorrhea, drying and thinning of the hair on the head with the development of hirsutism of the face and trunk. In the male sexual powers may be impaired. In addi-tion the blood pressure becomes elevated and eventually arterial changes of the malig-nant nephrosclerotic type are found. In a large proportion, but not all, carbohydrate tolerance is impaired. Osteoporosis, especially affecting the spine, is common. Since the appearance of Cushing's monograph the cases reported with this syn-drome have multiplied with great rapidity. However, in a large proportion, instead of basophilic tumors, hypertrophy or tumors of the adrenal cortex have been found.

DURING the short period of time that body-section roentgenography has been practised, the work of many investigators indicates that the thorax is an especially fertile field for diagnostic contributions by the method. Sectional films have demonstrated the relations of bronchi and pulmonary vessels (Grossmann, 9, 10; Chaoul, 5; Greineder, 8; McDougall and Crawford, 13). Studies of pulmonary tuberculosis with reference to gross distribution of the disease, recognition and localization of cavities, the effects of artificial pneumothorax and thoracoplasty, suggest the frequency with which planigraphy will be used in future roentgen studies of this disease. Mediastinal and pulmonary tumors have been studied by Moore (14, 15) who predicted the demonstration of intrabronchial tumors by sectional films. Laminagraphs of pulmonary tumors convincingly demonstrate the advantages of body-section roentgenography. Chaoul (5) has suggested that dilatations of the bronchi in bronchiectasis can be demonstrated without the ...

T HE only anatomical variants that have been generally recognized in infants born of diabetic mothers are excessive body weight and increase in the size and number of the islands of Langerhans. Their exact incidence is not known, but it is significantly greater than in the normal newborn infant population. In the present communication it will be shown that other important deviations from the normal anatomy of the newborn infant are to be found in some infants born to diabetic mothers; namely, a marked hypertrophy of the heart and an increase in the erythropoietic tissue of tile liver. In fact, we have observed that macrosomia, hyperp]asia of the islands of Langerhans, cardiac hypertrophy, and erythroblastosis occur together in tile same infant in a surprising number of cases. Our attention was directed to these findings by a recent study made in this clinic of six infants born to diabetic mothers2 Two of the infants had by roentgen examination considerable enlargement of their hearts in the first few days of life. Similar observations have been made here in four additional infants. The observations in these ten infants led us to search the literature and the autopsy files of the New Haven Hospital, the New York tIospital,* and the Boston Lying-In Hospital} for anatomical confirmation of the roentgen evidence of

IN view of the increased interest in the pituitary body in relation to experimental and clinical endocrinology, and because of the frequent attempts to influence disease through irradiation of the adenomatous or non-adenomatous gland, it has seemed important to study the effects of irradiation of the normal pituitary body of the white rat. During the past twenty years there have been numerous reports on the effects of irradiation of the hypophysis for various gynecological conditions, with varying results. Recently, irradiation of the pituitary has been extended to patients with diabetes mellitus and so-called essential hypertension, again with varying results. The question naturally arises, can the non-adenomatous pituitary gland be influenced with therapeutic doses of x-rays? A partial answer to this question could probably be obtained through animal experimentation. Apparently the first studies on the effects of pituitary irradiation in animals were made by Strauss (1) and Brunner (2), working independ...

The first case of congenital occlusion of the aqueduct of Sylvius was reported by Hilton in 1847. Pancoast, Pendergrass, and Schaeffer have stated in their classic work, “The Head and Neck in Roentgen Diagnosis,” that of all of the lesions revealed by ventriculography those obstructing the aqueduct are the most difficult to diagnose. Twining emphasized the danger of being misled by inadequate visualization of the aqueduct and fourth ventricle and discussed the hydrodynamics involved in filling these structures with air. Complete replacement of cerebrospinal fluid with air is seldom possible by ventricular puncture in the presence of a blocked ventricular system. The difficulties encountered, therefore, are largely technical and involve positional manipulation of the available air to establish the point of occlusion of the system. However, there are also the possibilities of an incomplete block of the aqueduct and unsatisfactory visualization of an air-filled aqueduct due to superimposed structures that ob...

Saralasin, an angiotensin II antagonist, was infused into 49 patients with renal artery stenosis, 10 patients with essential hypertension and normal renal arteriograms, and five patients with "low-renin essential hypertension." Renal venous renin and differential renal function studies were used to assess the functional significance of arterial stenoses. "Response" to saralasin, evidenced by a fall in blood pressure during infusion, occurred in no patients with "low renin" hypertension and in only 20% of patients with normal renal arteriograms. In contrast, saralasin "response" occurred in more than 80% of patients with renal artery stenosis and lateralizing functional studies and 100% of cases of "proven" renovascular hypertension (cure or improvement of hypertension after operative treatment). We suggest that saralasin infusion might be a valuable screening test for the recognition of renovascular hypertension.

The achievements of cardiovascular surgery during the last decade have stirred renewed interest in the diagnosis of congenital cardiovascular malformations, and extensive case-finding programs have been developed to aid in the recognition of those lesions amenable to surgical correction. Accurate clinical diagnosis is often difficult, and recourse to some of the new diagnostic technics by a team consisting of clinician, radiologist, and cardiovascular physiologist requires a concentration of talent and procedures that are time-consuming and expensive. From a practical standpoint, it is necessary to screen the large numbers of patients who present themselves for a consideration of surgical therapy and to separate those that can be easily recognized as amenable to surgical treatment from those requiring the additional studies upon which an evaluation of operability may be based. The roentgenol-ogist's recognition of the diagnostic capacities and limitations of conventional roentgenographic examinations will...

The introduction by Swick (27) in 1929 of excretory urography as a procedure for roentgenographic visualization of the urinary tract has led to improved clinical evaluation of renal function and diagnosis of renal lesions. During the past twenty years many new substances have been used as contrast media for diagnostic roentgenologic technics. This paper reviews our experience with Urokon Sodium 70%, a new contrast medium for excretory urography recently developed in the research laboratory of the Mallinckrodt Chemical Works. Urokon Sodium 70% is a sodium salt of 3-acetylamino-2,4,6-triiodobenzoic acid. It is reported to have the following structural formula, and to contain 65.8 per cent iodine per molecule (32). A number of earlier reports on the clinical use of this substance for intravenous injection as a 30 per cent solution for excretory urography indicate a lower incidence of severe side reactions than encountered with other compounds now widely used for the procedure. Pyelograms obtained following t...

The removal of a phrenic nerve to paralyze one-half of the diaphragm is now extensively performed in certain cases of pulmonary tuberculosis and in other conditions. Although the literature contains many statements to the effect that cough and expectoration are facilitated by phrenicectomy we have been unable to find any recorded experimental work dealing with such a result. Our experiments show that on the contrary the operation actually interferes with cough and diminishes the elimination from the lung of lipiodol injected into it.The efficiency of the cough mechanism was measured by the elimination of lipiodol from the lungs before and after phrenicectomy. The rate of disappearance of the oil was determined by means of fluoroscopy and serial roentgen-ray films. Experiments were performed upon 10 dogs. In 2 dogs the time required for the complete disappearance of the oil from the lung was determined. In these 2 dogs a unilateral phrenicectomy was performed after all the oil had disappeared. After they h...

Obstructive emphysema due to foreign bodies in the bronchi was described by Iglauer 1 in 1912. Since then, numerous articles on the localization of nonopaque foreign bodies through the presence of obstructive emphysema have appeared in the literature. Notable are those of Manges 2 and Jackson. 3 The recent work of Lindskog and Van Allen 4 on the experimental production of obstructive emphysema has greatly increased the knowledge of the physiology of the subject. They have shown that obstructive emphysema occurs whenever a main bronchus is obstructed by a one-way valve mechanism which permits the ingress of air during inspiration and retards its egress from the lobe during expiration. They found also that obstruction of a complete lobe is necessary for the production of obstructive emphysema. Because of collateral respiration, lobular expiratory obstruction is not followed by obstructive emphysema unless there is interference with the collateral respiration of the part