o bstruction of the superior vena cava produces a dramatic syndrome consisting of edema and plethora of the face, neck, and arms, engorgement of the veins in the neck, and the appearance of dilated, tortuous, superficial collateral veins on the arms, neck, and upper torso.’ The patient may also suffer from dyspnea and disturbance of the sensorium, both often worse in the recumbent position, and from stridor, hoarseness, visual disturbance, convulsions, suffusion of the conjunctiva, and proptosis.’ Venous pressures in the neck and arms are always increased and are greater than the pressures in the legs or right atrium and may be paradoxically increased with inspiration.1’2’6’7 The most common cause of the superior vena cava syndrome is bronchogenic carcinoma, accounting for 75 to 90 percent of all cases.4’8 A second common cause is lymphoma.4 Other neoplastic diseases cause most of the remaining cases,4 although the list of possible causes is long. Uncommon causes of the superior vena cava syndrome include metastatic cancer,4 aortic aneurysm (atherosclerotic or syphilitic ) ‘#{176} retrosternal goiter,7” mediastinitis (idiopathic, tuberculotic, histoplasmotic, actinomycotic, syphilitic, or pyogenic ) and iatrogenic causes (central venous catheter, wire of pacemaker, irradiation-induced pneumonitis, yen-

Asparaginase induced hemorrhagic pancreatitis is a rare but serious development occurring in less than 0.5% of patients treated with this drug. Severe pancreatitis with progressive abdominal distention, toxemia, hypotension and respiratory insufficiency occurred in an 18-year-old patient with acute lymphoblastic leukemia following treatment with asparaginase. There was a dramatic response to high flow peritoneal lavage with rapid recovery within 24 hours from a moribund state. The subsequent development of a pseudocyst, with progressive increase in size and development of obstructive symptoms, required surgical decompression. Transgastric cystogastrostomy was successfully carried out.

When superior vena caval obstruction complicates cancer of the lung; the prognosis is grave; 1 percent of such patients survive for one year. Improved palliation is reported from many radiation therapy centers using higher initial dose fractions and tumoricidal doses. We now report the findings in three patients with histologically confirmed bronchogenic carcinoma who had superior vena caval obstruction and who survived for nine years (two patients) and seven years (one patient). Aggressive therapy with irradiation seems to provide better palliation and may occasionally be associated with remarkably long survivals in this normally highly lethal disease.

Neocarzinostatin (NCZ), an acidic polypeptide antibiotic, was given to 47 patients with cancer and leukemia, and tolerance to two schedules, a single dose given as a 2 hour infusion and a continuous infusion over 5 days was investigated. Immediate reactions, including fever, chills, rigor, hypertension and mental confusion, were dose-limiting for the 2 hour infusion schedule, occurring at 3000 U/m2 and higher. Continuous administration for 5 days eliminated the immediate reactions and then hematological toxicity--often prolonged leukopenia and thrombocytopenia--became dose-limiting. Other toxicities of NCZ at both dose schedules included anemia, fever and chills, anorexia, nausea and vomiting, hepatic dysfunction, azotemia, hypophosphatemia, aminoaciduria, stomatitis, phlebitis and/or cellulitis at the venous infusion site and pruritus. Patients with solid tumors who had received little or no prior chemotherapy and had good bone marrow reserve tolerated up to 6000 U/m2/24 hours X 5 days. One patient with previously treated acute myelocytic leukemia was induced into a good partial remission lasting 10 weeks.

A 43-year-old man with a 36-year history of virilization due to an adrenal carcinoma is presented. The initial presentation at age 7 with precocious puberty and epiphyseal bone fusion suggested increased androgen effect at a very early age. The patient's 36-year course before his death suggested either a very slow growing adrenal carcinoma or untreated congenital adrenal hyperplasia that progressed to an adrenal carcinoma. Endocrine evaluation showed markedly increased DHEA and DHEA-sulfate levels. These were associated with elevated plasma and urinary estradiol levels and suppressed LH and FSH plasma concentrations. The 24-hour mean levels of cortisol and testosterone were normal. Studies of the circadian periodicity of cortisol showed a disturbed temporal pattern but a normal 24-hour mean concentration that correlated with a normal cortisol production rate. The 24-hour LH secretory pattern showed a decrease in the normal episodic fluctuation of this hormone over the 24-hour period.

Two adult men with feminizing adrenal cortical carcinoma had measurements of their 24-h plasma corticosteroid and gonadotropin patterns as well as 24-h mean hormone levels of estradiol, estetrol, 11-desoxycortisol, DHEA-S, DHEA and testosterone. Cortisol, 11-desoxycortisol and estrogen production rates were also measured. The 24-h corticosteroid patterns showed preservation of the normal 24-h episodic and circadian patterns, albeit at higher levels. The cortisol production rates were markedly elevated despite only moderate elevation of the 24-h mean cortisol level. There were elevated plasma 11-desoxycortisol levels and a markedly elevated 11-desoxycortisol production rate in one patient and THS excretion in the other. The plasma estradiol levels, urinary excretion and production rates were markedly elevated. In addition, there was a decrease in the specific activity of estriol compared with estrone and estradiol as well as measurable levels of estetrol in both patients. These latter observations coupled with the urinary immunoassayable hCG in one patient suggest that these tumors may be functioning like trophoblastic tissue. The possibility that estetrol may serve as an additional marker for tumors of trophoblastic origin is of additional interest.

After 1 week of a normal control (baseline) period, 7 healthy young adult subjects were subjected to a 3-hr sleep-wake schedule, (ultradian) which was adhered to for 10 days. They were allowed eight 1 hr sleep times, equally spaced throughout each 24 hr period. They were then allowed a normal nocturnal 8-hr sleep time for 7 days. During all lights-out sleep periods, poly-graphic definition of sleep stages and waking time was made. On the sixth 24-hr period of the first week (baseline) and on the eighth 24-hr period of the ultradian period, sequential 20-min plasma samples were obtained by means of an indwelling intravenous catheter. Rectal temperature was obtained at regularly spaced frequent intervals. Despite significant sleep deprivation, a circadian pattern of total sleep time persisted throughout the 10-day ultradian condition. The distribution and amount of REM sleep time was most affected with stages 3–4 sleep least affected. The time of maximum sleep was delayed by approximately 6 hr. The temporal pattern of the secretory episodes of cortisol and the body temperature curves demonstrated a persistence of the 24-hr (circadian) periodicity for all subjects during the ultradian condition. A 3-hr cortisol cycle was superimposed on the 24-hr pattern. This 3-hr cycle was entrained to the 3-hr sleep-waking cycle such that low plasma concentrations of cortisol were associated with the dark (sleep) period and high concentrations with the first hour after "lights on." No correlation could be demonstrated between a specific sleep stage and the subsequent release of hormone even though a correlation was present for total sleep. The mean 24-hr output of GH was not different for the baseline and ultradian conditions. However, the sharp peak of GH secretion found between 11 PM to 1 AM in the baseline condition was not present in the ultradian condition. The persistence of a 24-hr temperature curve, sleep-waking cycle and cortisol pattern in spite of the attempt to disrupt these functions for 10 days demonstrates the highly resistant nature of these systems.

Plasma cortisol was measured for seven 24-hr periods using the frequent sampling technique (every 20 min) in 6 normal acclimated subjects. A defined sleep-wake schedule was established over 3–5 consecutive nights with polygraphic definition of their sleep patterns. A mean of 9 secretory episodes (range 7–13) occurred over the 24-hr sampling time, the subjects spending an average of 24% of the time in active secretion. It was estimated that, on the average, 16 mg of cortisol was secreted over the 24 hr, with a mean of 66 min half-life of cortisol decay. Although great variability was found in both the amount of cortisol secreted and the time spent in secretory activity/hr, the secretory rate was quite constant at approximately .05 mg/min. A temporal pattern of episodic secretion was recognized, and the 24-hr sleep-wake cycle could be divided into 4 unequal temporal phases: Phase 1. A 6-hr period of “minimal secretory activity” (4 hr before and 2 hr after lights out); Phase 2. A 3-hr period called “preliminary nocturnal secretory episode” (3rd to 5th hr of sleep); Phase 3. A 4-hr period, the “main secretory phase” (6, 7, 8 hr of sleep and 1st hr after awakening); and Phase 4. The 11 hr of “intermittent waking secretory activity.” No evidence for a “basal level” or “steady state” of cortisol concentration was found. Changes in cortisol output during the 24-hr day appear to be due to differences in frequency and duration of secretory episodes and not to major changes in secretory rate.

PAST studies of the sleep-waking circadian cycle in man emphasized the temporal relationship to other rhythmic physiological and chemical functions.1It was implicitly assumed in these studies that sleep is a unitary process. Recent evidence, however, clearly indicates that sleep is composed of recurring short-term physiologic events.2,3In man, during each daily sleep period, a consistent sequence of sleep patterns occurs, characterized by four or five recurrent 90-minute cycles. Future studies of circadian phase relationships between sleep and physiologic variables should take into account the qualitative and quantitative differences between sleep stage patterns. We have begun to study the time relation of sleep stages and neuroendocrine processes.4The method of cycle phase shift of 180° (sleep-waking cycle inversion) has been used in man.5-8This report describes the changes in sleep pattern when normal young adults were subjected to an acute inversion of sleep-waking cycles in