Bilateral pneumonia and inappropriate secretion of antidiuretic hormone in a premature infant Apostolos N.
Papageorgiou,*
A 6-week-old infant born
md,
prematurely
had severe hyponatremia and other features of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). This disturbance was believed to be secondary to extensive bilateral pneumonia with collapse of the right upper lobe. Although this association has been recognized in adults, this is the first report of its occurrence in an infant. SIADH must be considered in the differential diagnosis of hyponatremia in association with pneumonia in an infant. Un enfant de 6 semaines, ne prematurement, a presente une hyponatremie severe et d'autres manifestations du syndrome de secretion insuffisante d'hormone
antidiuretique (SIHAD). On a cru perturbation ait pu etre reliee a une pneumonie bilaterale
que cette
etendue
avec
affaissement du lobe
superieur droit. Bien qu'une telle
association ait deja ete identifiee chez I'adulte, c'est la premiere fois qu'elle est signalee chez un nourrisson. Ce syndrome doit etre considere
dans le
diagnostic differentiel de I'hyponatremie associee a une
pneumonie chez le nourrisson.
Since the original description by Schwartz and associates1 in 1957, the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) has been recognized with increasing fre¬ quency. The syndrome has been most commonly described in association with
frcp[c];
Michael
MoFFAixt
md
newborn infants receiving mechanical ventilation. We report a case of SIADH in a premature infant with bilateral pneu¬ monia, probably of viral origin. Al¬ though pneumonia is a known cause of this syndrome in adults,6 we believe this to be the first well documented case in a
neonate.
Case
report
A 6-week-old boy was admitted to hos¬ pital with a 5-day history of coryza, cough and conjunctivitis. One day prior to ad¬ mission, lethargy, poor feeding and a weak cry had been noted by the mother. Six hours prior to admission the baby had vomited once after feeding. There had been no other episode of vomiting or any diarrhea. The formula had been taken in adequate amounts until the day before admission and the mother had been pre¬ paring the formula correctly. An older brother had had a similar upper respira¬ tory tract infection the week before and the mother had a slight cold when the infant was admitted. The baby was born at the Jewish Gen¬ eral Hospital at 32 weeks* gestation, weigh¬ ing 1600 g; the mother's membranes had been ruptured for 5 days. He had been taken home after 4 weeks, during which time there had been no complications; weight gain was rapid and at discharge he weighed 2200 g. One week after discharge he weighed 2410 g and was doing well. On admission the infant appeared very ill; his skin was ashen and he was lethargic and responded poorly to stimuli. Temper¬ ature was 35.6°C; respiratory rate, 60/ min; and heart rate, 120 beats/min.
Weight
was 3000 g; head circumference, 34 cm; and length, 50 cm. The anterior fontanelle was small and soft and the sutures were normal. The mucus mem¬ branes were moist and the skin turgor was normal. There was obvious intercostal indrawing. The respiratory pattern was peri¬ odic and fine rales were heard throughout both lungs. The systolic blood pressure was 80 mm Hg. The heart sounds were normal and there was no murmur. The liver was palpable 2 cm below the right costal margin. The penis and scrotum were normal in colour and size and both testicles were palpable in the scrotum. The grasp reflex was normal but sucking was poor and a Moro reflex could not be elicited. The hemoglobin value was 9 g/dl; the leukocyte count, 13.4 x 109// (segmented neutrophils, 0.5; bands, 5.3; small lym¬ phocytes, 5.5; large lymphocytes, 12.0; and monocytes, 0.9 x 109//); and the platelet count, 457 x 109//. A peripheral blood smear showed polychromasia of the ery¬ throcytes with anisopoikilocytosis and few atypical lymphocytes. The blood glucose value was 120 mg/dl and the blood urea nitrogen (BUN) value, 9 mg/dl. Serum electrolyte values and serum (and urine) osmolality are shown in Table I. Plasma cortisol values at 12 hours and 24 hours after admission were 37 and 11.25 Mg/dl, respectively. An arterialized capillary blood sample, taken while the patient was breathing 30% oxygen, showed the fol¬ lowing values: hydrogen ion, 68 nmol// (pH, 7.17); Pco2, 74 mm Hg; base excess, .2.5 mmol//; actual bicarbonate, 24 mmol//; Po2, 34 mm Hg; and oxygen satu¬
ration, 49%. Urinalysis showed a trace of protein and six to eight erythrocytes per high power
nervous system (CNS) disease,2 Table I.Changes in serum and urine data and weight during first 48 hours of bronchogenic carcinoma,3 pulmonary hospitalization of infant with pneumonia and inappropriate secretion and CNS tuberculosis4 and administra¬ of antidiuretic hormone tion of certain drugs.5 Recently it has 8h after 24 h after 48 h after been suggested that SIADH may occur Admission admission admission admission in the neonatal period as a consequence Variable of CNS disturbance due to traumatic delivery or hypoxia, or both, and in
central
From the departments of pediatrics and neonatology of the Montreal Children's Hospital and the Jewish General Hospital, McGill University *Neonatologist-in-charge, Jewish General Hospital; attending pediatrician and neonatologist, Montreal Children's Hospital; assistant professor of pediatrics, McGill University tSenior resident in pediatrics, Montreal Children's Hospital Reprint requests to: Dr. A. Papageorgiou, Department of neonatology, Jewish General Hospital, 3755 Cote Ste. Catherine Rd., Montreal, PQ H3T 1E2
CMA JOURNAL/JUNE 19, 1976/VOL. 114 1119
field but no leukocytes. Stool trypsin value was 220 .tg/g and chymotrypsin value, 770 .'g/g. Cerebrospinal fluid (CSF) was clear; the glucose value was 76 mg/dl and the protein value, 63.5 mg/dl; there were no leukocytes and the erythrocyte count was 5.6 x 108/i. Cultures of the CSF, blood, urine and throat and stool swabs failed to grow bacteria. Viral tissue cultures of nasopharyngeal aspirate grew respiratory syncytial virus (RSV) but titres of antibody to RSV on admission and 2 weeks later were positive at the same dilution, 1:8. Results of the sweat test, done twice, were normal. The chest radiograph showed collapse of the right upper lobe with mild right middle lobe consolidation and minimal left lower lobe consolidation (Fig. 1). The tentative diagnosis was bilateral pneumonia with inappropriate secretion of ADH. The baby was placed in a warm incubator in 50% oxygen. Gentamicin and ampicillin were given intravenously. Fluid therapy was initiated with normal saline, but 4 hours later the baby had a generalized convulsion, which ceased with intravenous infusion of 1 mg cf diazepam. The serum sodium value at that time was 113 mmol/l but the value increased to 124 mmol/l with the intravenous infusion of 40 ml of 3% saline over 1 hour, followed by restriction of fluids to replacement of insensible water losses plus the volume of urine excreted. Urine was collected in 8-hour aliquots for measurement of electrolytes, specific gravity and osmolality. By the 2nd hospital day the serum electrolyte values were normal, the hypothermia had resolved and the blood gas values had improved (hydrogen ion, 42 nmol/l [pH, 7.28]; Pco2, 40 mm Hg). The baby's condition improved steadily after the 3rd day and oral feedings were slowly introduced. The electrolyte values remained normal throughout the remainder of the hospital *stay and there were no further convulsions. Antibiotic therapy was continued for 8 days. The only complication during the acute phase of the illness was the development of gross hematuria on the 2nd day; microscopic hematuria persisted for 7 days and then disappeared. There were no casts in the urine, and the BUN and serum creatinine values remained normal. At follow-up 6 weeks after discharge the infant was gaining weight and developing normally. An electroencephalogram and an intravenous pyelogram were normal.
FIG. 1-Mild pneumonia of right middle and left lower lobes and more severe pneumonia with partial collapse of right upper lobe in 6-week-old boy.
Discussion Stormont and Waterhouse7 were the first to recognize the association of pneumonia and SIADH - in a 69year-old woman with staphylococcal pneumonia who had a serum sodium concentration of 103 mmol/l. The mechanisms by which acute bacterial or viral pneumonia may lead to inappropriately increased production of ADH are not well established. However, it has been shown in animals that the regulation of ADH release is governed by changes in effective intravascular fluid volume8 and also by the osmolality of the extracellular fluid.9 Also, stress, emotional factors, pain and certain drugs may, through the hypothalamohypophyseal system,10 stimulate the release of ADH. Finally, baroreceptors in the aorta, carotid sinus and carotid bodies seem to participate in the regulation of ADH secretion." Zehr, Johnson and Moore12 have shown, in sheep, that there is a relation between left atrial stretch and ADH release. In human beings, situations that tend to alter left atrial filling affect ADH secretion: ventilation by positivepressure respirators,13 quiet standing and elevated ambient temperatures14 tend to decrease left atrial filling by causing blood to pool in peripheral vascular beds and thus promote release of ADH. The converse is also true: when left atrial filling increases, the production of ADH decreases. It is possible that the same mechanism may operate in severe pneumonia. Because of the decreased blood flow through the pulmonary vascular bed there is inadequate filling of the left atrium and, consequently, an increase in ADH secretion. Studies by Benson and associates15 and Kumar and colleagues16 in patients with pneumonia demonstrated decreased cardiac output on the basis of increased arteriovenous oxygen difference and inadequate tissue perfusion. The severe hypoxia in our patient (Pa2, 34 mm Hg in 30% 02) may have produced pulmonary vasoconstriction, which in turn was responsible for the reduced blood return to the left atrium. This mechanism may be particularly important in preniature infants. It is also possible that, as has been demonstrated in tuberculosis, an ADH-like substance is elaborated by the affected lung tissue.17 The abnormal production of ADH seems to be particularly acute in severe pneumonia, as was demonstrated in our patient and indicated in previous reports.6 An additional reason for the hyponatremia may be the fact that decreased cardiac output leads to retention of water and further dilution of serum sodium.
1120 CMA JOURNAL/JUNE 19, 1976/VOL. 114
Although we failed to demonstrate the presence of increasing titres of antibody to RSV, the presence of the virus in the tracheal aspirate and the history of upper respiratory tract infection in the family in the days preceding the patient's hospitalization, together with the negative bacterial cultures, lead one to believe that the cause of the pneumonia was most likely viral. The hematuria remains unexplained, but an interesting speculation is that the same virus caused cystitis. We thank Drs. P.H. Beaudry and K.N. Drummond for critical review of the manuscript and useful suggestions.
References 1. SCHWARTZ WB, BENNEI-F W, CUSELOP 5, et
al: A syndrome of renal sodium loss and hyponatremia probably resulting from inappropriate secretion of antidiuretic hormone. Am J Med 23: 529, 1957
2. CARTER NW, RECTOR FC Ja,
SELDIN
PW:
Hyponatremia in cerebral disease resulting from the inappropriate secretion of antidiuretic hormone. N Engi J Med 264: 67, 1961 3. SEGAR WE, Mooaa WW: Hyponatremia. Increased antidiuretic hormone and "inappropriate" thirst in a patient with bronchogenic carcinoma. Mtnn Med 51: 625, 1968 4. SHALHOUB RJ, ANTornou LD: The mechanism of hyponatremia in pulmonary tuberculosis. Ann intern Med 70: 943, 1969 5. MosEs AM, MILLER M: Drug-induced dilutional hyponatremia. N Engi I Med 291: 1234, 1974 6. RosENow ED, SEGAR WE, ZEHR JE: Inappropriate antidiuretic hormone secretion in pneumonia. Mayo Clin Proc 47: 169, 1972 7. STORMONT JM, WATERHOUSE C: Severe hyponatremia associated with pneumonia. Metabolism 11: 1181, 1962 8. SISARa L: Acute reduction in extracellular fluid volume and the concentration of antidiuretic hormone in blood. Endocrinology 69: 925, 1961 9. ARNDT JO, GAUER OH: Diuresis induced by water infusion into the carotid loop of unanesthetized dogs. Arch Physiol 282: 301, 1965 10. MILLS E, WANG SC: Liberation of antidiuretic hormone: pharmacologic blockade of ascending pathways. Am I Physlol 207: 1405, 1964 11. SHARE L, LEvY NM: Cardiovascular receptors and blood titer of antidiuretic hormone. Am I Physiol 203: 425, 1962 12. ZEHR JE, JOHNSON JA, Mooaa WW: Left atrial pressure, plasma osmolality, and ADH levels in the unanesthetized ewe. Am I Physiol 217: 1672, 1969 13. SLADEN A, LAYER MB, PANTOPPIDAU H: Pul-
monary complications and water retention in prolonged mechanical ventilation. N Engl I Med 279: 448, 1968
14. SEGAR WE, Moosa WW: The regulation of antidiuretic hormone release in man. Effects of change in position and ambient temperature on blood ADH levels. I Clin Invest 47: 2143, 1968 15. BENSON H, A5CBARIAN M, ADLER LN, et al: Hemodynamic effects of pneumonia. I. Normal and hypodynamic responses. I Clin Invest 49: 791, 1970 16. KuMut R, WALLACE WA, RAMIRax A, et al: Hemodynamic effects of pneumonia. IL ExpEnsion of plasma volume. Ibid, p 799 17. VORHERK H, MASSRY SO, FALLET R, et al:
Antidiuretic principle in tuberculous lung tissue of a patient with pulmonary tuberculosis and hyponatremia. Ann Intern Med 72: 383, 1970
Papageorgiou,*
A 6-week-old infant born
md,
prematurely
had severe hyponatremia and other features of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). This disturbance was believed to be secondary to extensive bilateral pneumonia with collapse of the right upper lobe. Although this association has been recognized in adults, this is the first report of its occurrence in an infant. SIADH must be considered in the differential diagnosis of hyponatremia in association with pneumonia in an infant. Un enfant de 6 semaines, ne prematurement, a presente une hyponatremie severe et d'autres manifestations du syndrome de secretion insuffisante d'hormone
antidiuretique (SIHAD). On a cru perturbation ait pu etre reliee a une pneumonie bilaterale
que cette
etendue
avec
affaissement du lobe
superieur droit. Bien qu'une telle
association ait deja ete identifiee chez I'adulte, c'est la premiere fois qu'elle est signalee chez un nourrisson. Ce syndrome doit etre considere
dans le
diagnostic differentiel de I'hyponatremie associee a une
pneumonie chez le nourrisson.
Since the original description by Schwartz and associates1 in 1957, the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) has been recognized with increasing fre¬ quency. The syndrome has been most commonly described in association with
frcp[c];
Michael
MoFFAixt
md
newborn infants receiving mechanical ventilation. We report a case of SIADH in a premature infant with bilateral pneu¬ monia, probably of viral origin. Al¬ though pneumonia is a known cause of this syndrome in adults,6 we believe this to be the first well documented case in a
neonate.
Case
report
A 6-week-old boy was admitted to hos¬ pital with a 5-day history of coryza, cough and conjunctivitis. One day prior to ad¬ mission, lethargy, poor feeding and a weak cry had been noted by the mother. Six hours prior to admission the baby had vomited once after feeding. There had been no other episode of vomiting or any diarrhea. The formula had been taken in adequate amounts until the day before admission and the mother had been pre¬ paring the formula correctly. An older brother had had a similar upper respira¬ tory tract infection the week before and the mother had a slight cold when the infant was admitted. The baby was born at the Jewish Gen¬ eral Hospital at 32 weeks* gestation, weigh¬ ing 1600 g; the mother's membranes had been ruptured for 5 days. He had been taken home after 4 weeks, during which time there had been no complications; weight gain was rapid and at discharge he weighed 2200 g. One week after discharge he weighed 2410 g and was doing well. On admission the infant appeared very ill; his skin was ashen and he was lethargic and responded poorly to stimuli. Temper¬ ature was 35.6°C; respiratory rate, 60/ min; and heart rate, 120 beats/min.
Weight
was 3000 g; head circumference, 34 cm; and length, 50 cm. The anterior fontanelle was small and soft and the sutures were normal. The mucus mem¬ branes were moist and the skin turgor was normal. There was obvious intercostal indrawing. The respiratory pattern was peri¬ odic and fine rales were heard throughout both lungs. The systolic blood pressure was 80 mm Hg. The heart sounds were normal and there was no murmur. The liver was palpable 2 cm below the right costal margin. The penis and scrotum were normal in colour and size and both testicles were palpable in the scrotum. The grasp reflex was normal but sucking was poor and a Moro reflex could not be elicited. The hemoglobin value was 9 g/dl; the leukocyte count, 13.4 x 109// (segmented neutrophils, 0.5; bands, 5.3; small lym¬ phocytes, 5.5; large lymphocytes, 12.0; and monocytes, 0.9 x 109//); and the platelet count, 457 x 109//. A peripheral blood smear showed polychromasia of the ery¬ throcytes with anisopoikilocytosis and few atypical lymphocytes. The blood glucose value was 120 mg/dl and the blood urea nitrogen (BUN) value, 9 mg/dl. Serum electrolyte values and serum (and urine) osmolality are shown in Table I. Plasma cortisol values at 12 hours and 24 hours after admission were 37 and 11.25 Mg/dl, respectively. An arterialized capillary blood sample, taken while the patient was breathing 30% oxygen, showed the fol¬ lowing values: hydrogen ion, 68 nmol// (pH, 7.17); Pco2, 74 mm Hg; base excess, .2.5 mmol//; actual bicarbonate, 24 mmol//; Po2, 34 mm Hg; and oxygen satu¬
ration, 49%. Urinalysis showed a trace of protein and six to eight erythrocytes per high power
nervous system (CNS) disease,2 Table I.Changes in serum and urine data and weight during first 48 hours of bronchogenic carcinoma,3 pulmonary hospitalization of infant with pneumonia and inappropriate secretion and CNS tuberculosis4 and administra¬ of antidiuretic hormone tion of certain drugs.5 Recently it has 8h after 24 h after 48 h after been suggested that SIADH may occur Admission admission admission admission in the neonatal period as a consequence Variable of CNS disturbance due to traumatic delivery or hypoxia, or both, and in
central
From the departments of pediatrics and neonatology of the Montreal Children's Hospital and the Jewish General Hospital, McGill University *Neonatologist-in-charge, Jewish General Hospital; attending pediatrician and neonatologist, Montreal Children's Hospital; assistant professor of pediatrics, McGill University tSenior resident in pediatrics, Montreal Children's Hospital Reprint requests to: Dr. A. Papageorgiou, Department of neonatology, Jewish General Hospital, 3755 Cote Ste. Catherine Rd., Montreal, PQ H3T 1E2
CMA JOURNAL/JUNE 19, 1976/VOL. 114 1119
field but no leukocytes. Stool trypsin value was 220 .tg/g and chymotrypsin value, 770 .'g/g. Cerebrospinal fluid (CSF) was clear; the glucose value was 76 mg/dl and the protein value, 63.5 mg/dl; there were no leukocytes and the erythrocyte count was 5.6 x 108/i. Cultures of the CSF, blood, urine and throat and stool swabs failed to grow bacteria. Viral tissue cultures of nasopharyngeal aspirate grew respiratory syncytial virus (RSV) but titres of antibody to RSV on admission and 2 weeks later were positive at the same dilution, 1:8. Results of the sweat test, done twice, were normal. The chest radiograph showed collapse of the right upper lobe with mild right middle lobe consolidation and minimal left lower lobe consolidation (Fig. 1). The tentative diagnosis was bilateral pneumonia with inappropriate secretion of ADH. The baby was placed in a warm incubator in 50% oxygen. Gentamicin and ampicillin were given intravenously. Fluid therapy was initiated with normal saline, but 4 hours later the baby had a generalized convulsion, which ceased with intravenous infusion of 1 mg cf diazepam. The serum sodium value at that time was 113 mmol/l but the value increased to 124 mmol/l with the intravenous infusion of 40 ml of 3% saline over 1 hour, followed by restriction of fluids to replacement of insensible water losses plus the volume of urine excreted. Urine was collected in 8-hour aliquots for measurement of electrolytes, specific gravity and osmolality. By the 2nd hospital day the serum electrolyte values were normal, the hypothermia had resolved and the blood gas values had improved (hydrogen ion, 42 nmol/l [pH, 7.28]; Pco2, 40 mm Hg). The baby's condition improved steadily after the 3rd day and oral feedings were slowly introduced. The electrolyte values remained normal throughout the remainder of the hospital *stay and there were no further convulsions. Antibiotic therapy was continued for 8 days. The only complication during the acute phase of the illness was the development of gross hematuria on the 2nd day; microscopic hematuria persisted for 7 days and then disappeared. There were no casts in the urine, and the BUN and serum creatinine values remained normal. At follow-up 6 weeks after discharge the infant was gaining weight and developing normally. An electroencephalogram and an intravenous pyelogram were normal.
FIG. 1-Mild pneumonia of right middle and left lower lobes and more severe pneumonia with partial collapse of right upper lobe in 6-week-old boy.
Discussion Stormont and Waterhouse7 were the first to recognize the association of pneumonia and SIADH - in a 69year-old woman with staphylococcal pneumonia who had a serum sodium concentration of 103 mmol/l. The mechanisms by which acute bacterial or viral pneumonia may lead to inappropriately increased production of ADH are not well established. However, it has been shown in animals that the regulation of ADH release is governed by changes in effective intravascular fluid volume8 and also by the osmolality of the extracellular fluid.9 Also, stress, emotional factors, pain and certain drugs may, through the hypothalamohypophyseal system,10 stimulate the release of ADH. Finally, baroreceptors in the aorta, carotid sinus and carotid bodies seem to participate in the regulation of ADH secretion." Zehr, Johnson and Moore12 have shown, in sheep, that there is a relation between left atrial stretch and ADH release. In human beings, situations that tend to alter left atrial filling affect ADH secretion: ventilation by positivepressure respirators,13 quiet standing and elevated ambient temperatures14 tend to decrease left atrial filling by causing blood to pool in peripheral vascular beds and thus promote release of ADH. The converse is also true: when left atrial filling increases, the production of ADH decreases. It is possible that the same mechanism may operate in severe pneumonia. Because of the decreased blood flow through the pulmonary vascular bed there is inadequate filling of the left atrium and, consequently, an increase in ADH secretion. Studies by Benson and associates15 and Kumar and colleagues16 in patients with pneumonia demonstrated decreased cardiac output on the basis of increased arteriovenous oxygen difference and inadequate tissue perfusion. The severe hypoxia in our patient (Pa2, 34 mm Hg in 30% 02) may have produced pulmonary vasoconstriction, which in turn was responsible for the reduced blood return to the left atrium. This mechanism may be particularly important in preniature infants. It is also possible that, as has been demonstrated in tuberculosis, an ADH-like substance is elaborated by the affected lung tissue.17 The abnormal production of ADH seems to be particularly acute in severe pneumonia, as was demonstrated in our patient and indicated in previous reports.6 An additional reason for the hyponatremia may be the fact that decreased cardiac output leads to retention of water and further dilution of serum sodium.
1120 CMA JOURNAL/JUNE 19, 1976/VOL. 114
Although we failed to demonstrate the presence of increasing titres of antibody to RSV, the presence of the virus in the tracheal aspirate and the history of upper respiratory tract infection in the family in the days preceding the patient's hospitalization, together with the negative bacterial cultures, lead one to believe that the cause of the pneumonia was most likely viral. The hematuria remains unexplained, but an interesting speculation is that the same virus caused cystitis. We thank Drs. P.H. Beaudry and K.N. Drummond for critical review of the manuscript and useful suggestions.
References 1. SCHWARTZ WB, BENNEI-F W, CUSELOP 5, et
al: A syndrome of renal sodium loss and hyponatremia probably resulting from inappropriate secretion of antidiuretic hormone. Am J Med 23: 529, 1957
2. CARTER NW, RECTOR FC Ja,
SELDIN
PW:
Hyponatremia in cerebral disease resulting from the inappropriate secretion of antidiuretic hormone. N Engi J Med 264: 67, 1961 3. SEGAR WE, Mooaa WW: Hyponatremia. Increased antidiuretic hormone and "inappropriate" thirst in a patient with bronchogenic carcinoma. Mtnn Med 51: 625, 1968 4. SHALHOUB RJ, ANTornou LD: The mechanism of hyponatremia in pulmonary tuberculosis. Ann intern Med 70: 943, 1969 5. MosEs AM, MILLER M: Drug-induced dilutional hyponatremia. N Engi I Med 291: 1234, 1974 6. RosENow ED, SEGAR WE, ZEHR JE: Inappropriate antidiuretic hormone secretion in pneumonia. Mayo Clin Proc 47: 169, 1972 7. STORMONT JM, WATERHOUSE C: Severe hyponatremia associated with pneumonia. Metabolism 11: 1181, 1962 8. SISARa L: Acute reduction in extracellular fluid volume and the concentration of antidiuretic hormone in blood. Endocrinology 69: 925, 1961 9. ARNDT JO, GAUER OH: Diuresis induced by water infusion into the carotid loop of unanesthetized dogs. Arch Physiol 282: 301, 1965 10. MILLS E, WANG SC: Liberation of antidiuretic hormone: pharmacologic blockade of ascending pathways. Am I Physlol 207: 1405, 1964 11. SHARE L, LEvY NM: Cardiovascular receptors and blood titer of antidiuretic hormone. Am I Physiol 203: 425, 1962 12. ZEHR JE, JOHNSON JA, Mooaa WW: Left atrial pressure, plasma osmolality, and ADH levels in the unanesthetized ewe. Am I Physiol 217: 1672, 1969 13. SLADEN A, LAYER MB, PANTOPPIDAU H: Pul-
monary complications and water retention in prolonged mechanical ventilation. N Engl I Med 279: 448, 1968
14. SEGAR WE, Moosa WW: The regulation of antidiuretic hormone release in man. Effects of change in position and ambient temperature on blood ADH levels. I Clin Invest 47: 2143, 1968 15. BENSON H, A5CBARIAN M, ADLER LN, et al: Hemodynamic effects of pneumonia. I. Normal and hypodynamic responses. I Clin Invest 49: 791, 1970 16. KuMut R, WALLACE WA, RAMIRax A, et al: Hemodynamic effects of pneumonia. IL ExpEnsion of plasma volume. Ibid, p 799 17. VORHERK H, MASSRY SO, FALLET R, et al:
Antidiuretic principle in tuberculous lung tissue of a patient with pulmonary tuberculosis and hyponatremia. Ann Intern Med 72: 383, 1970
