In vivo and in vitro studies on multidirectional mechanism of anti-allergic activity of budesonide.

Most studies on the effects of glucocorticosteroid therapy in rhinitis relate to their inhibitory effect on activation and the number of inflowing cells that are involved in the development and maintenance of inflammation. It is also very important to determine the range of effect of budesonide on residing cells (epithelial cells). The purpose of this study was to evaluate the effect of local budesonide therapy on the cytological image of the nasal mucosa, with attention paid to columnar cells in patients with rhinitis. The in vivo results obtained were analyzed in correlation with changes in normal CHO-K1 cells exposed to budesonide at concentrations falling within the pharmacological dose range. Fifty patients diagnosed with rhinitis with suspected allergic background without nasal polyps were included in clinical trials. The control group were 10 healthy people without clinical signs of rhinitis. Only in patients with homogeneous cytological picture, exfoliative cytology was performed before treatment and after 4 weeks of therapy with budesonide used in aerosol form. Papanicolaou and Pappenheim - stained smears were evaluated qualitatively and quantitatively for changes in nasal mucosal cells. The nasal mucosal image of the patients before treatment clearly indicated the pathological state confirmed by the presence of numerous neutrophils, eosinophils, abundant bacterial flora and goblet or epithelial cells prevalence. In contrast, in smears of patients post-treatment budesonide observed a clear improvement in their nasal mucosa by reducing inflammation. There was a significant increase in the number of columnar cells and the appearance of very numerous epithelial cells with increased cytoplasmic vacuolization and visible leucophagocytosis. In vitro studies were performed on normal CHO-K1 cells that were treated with budesonide at concentrations of 0.5 µM - 45 µM. After 48 hours of incubation with the test agent, the samples were prepared for optical microscopy using the H&E method and transmission electron microscopy. Comparison of cells exposed to budesonide with control cells (without addition of test agent) revealed vacuolization changes with autophagy. Apoptotic changes have also been demonstrated, which occured to a lesser extent than vacuolization. The changes observed after budesonide treatment in the cytological picture of patients with allergic rhinitis indicate the therapeutic effect of this drug. On the other hand, the changes observed in the cytoplasm of epithelial cells, such as autophagy (clearly promoted in CHO-K1 cells) and leucophagocytosis, may indicate an additional mechanism of action for budesonide.

Myocardial lactate metabolism in fetal and newborn lambs.

BACKGROUND: Around birth, myocardial substrate supply changes from carbohydrates before birth to primarily fatty acids after birth. Parallel to these changes, the myocardium is expected to switch from the use of primarily lactate before birth to fatty acids thereafter. However, myocardial lactate uptake and oxidation around birth has not been measured in vivo. METHODS AND RESULTS: We measured myocardial lactate uptake, oxidation, and release with infusion of [1-13C]lactate and myocardial flux of fatty acids and glucose in chronically instrumented fetal and newborn (1 to 15 days) lambs. Myocardial lactate oxidation was the same in newborn (81.7+/-14.7 micromol. min-1. 100 g-1, n=11) as in fetal lambs (60.7+/-26.7 micromol. min-1. 100 g-1, n=7). Lactate uptake was also the same in newborn as in fetal lambs. Lactate uptake was higher than lactate flux, indicating lactate release simultaneously with uptake. In the newborn lambs, lactate uptake declined with age. Lactate uptake was strongly related to lactate supply, whereas lactate oxidation was not. The supply of fatty acids or glucose did not interfere with lactate uptake, but the flux of fatty acids was inversely related to lactate oxidation. CONCLUSIONS: We show that lactate is an important energy source for the myocardium before birth as well as in the first 2 weeks after birth in lambs. We also show that there is release of lactate by the myocardium simultaneously with uptake of lactate. Furthermore, we show that lactate oxidation may be attenuated by fatty acids but not by glucose, probably at the level of pyruvate dehydrogenase.

Perinatal changes in myocardial metabolism in lambs.

BACKGROUND: Lactate accounts for a third of myocardial oxygen consumption before and in the first 2 weeks after birth. It is unknown how the remainder of myocardial oxygen is consumed. Glucose is thought to be important before birth, whereas long-chain fatty acids (LC-FA) are the prime substrate for the adult. However, the ability of the myocardium of the newborn to use LC-FA has been doubted. METHODS AND RESULTS: We measured the myocardial metabolism of glucose and LC-FA with [U-(13)C]glucose and [1-(13)C]palmitate in chronically instrumented fetal and newborn lambs. In fetal lambs, myocardial oxidation of glucose was high and that of LC-FA was low. Glucose and LC-FA accounted for 48+/-4% and 2+/-2% of myocardial oxygen consumption, respectively. In newborn lambs, oxidation of glucose decreased, whereas oxidation of LC-FA increased. Glucose and LC-FA accounted for 12+/-3% and 83+/-19% of myocardial oxygen consumption. To test whether near-term fetal lambs could use LC-FA, we increased the supply of LC-FA with a fat infusion. In fetal lambs during fat infusion, the oxidation of LC-FA increased 15-fold. Although the oxidation of LC-FA was still lower than in newborn lambs, the contribution to myocardial oxygen consumption (70+/-13%) was the same as in newborn lambs. CONCLUSIONS: These data show that glucose and lactate account for the majority of myocardial oxygen consumption in fetal lambs, whereas in newborn lambs, LC-FA and lactate account for the majority of myocardial oxygen consumption. Moreover, we showed that the fetal myocardium can use LC-FA as an energy substrate.

Spondylectomy for malignant tumors of the spine.

Spondylectomy is the complete surgical removal of all parts of one or more vertebrae above the sacrum. We report our initial experience with spondylectomy in eight patients with malignant tumors of the spine operated on over a 7-year period (1980 to 1986). Four patients had primary neoplasms of the spine, and four others had solitary metastases to the vertebrae. Following surgery, five patients underwent radiation therapy (RT) and chemotherapy depending on histology of the tumor. Radiographic confirmation of tumor resection was obtained on all patients. Pain relief was noted in all patients, and six patients with preoperative neurological deficits improved. There was no surgical mortality, and one patient developed wound dehiscence following surgery. Six of the eight patients are alive with a median follow-up of 36 months, and local control was achieved in six of the eight patients. These preliminary data suggest that malignant tumors of the spine can be completely resected using a staged approach. In potentially responsive tumors, systemic chemotherapy is recommended between the two operations to reduce the risk of systemic dissemination.

Inability of computed tomography appearance of recurrent malignant astrocytoma to predict survival following reoperation.

Computed tomographic (CT) scans of 39 patients who underwent reoperation for recurrent malignant astrocytoma at Memorial Sloan-Kettering Cancer Center from 1980 through 1987 were reviewed and correlated with the patients' clinical course. Histologic diagnosis (anaplastic astrocytoma v glioblastoma multiforme) had a statistically significant impact on survival following reoperation (P = .038). Patients with high preoperative performance status (P = .29), total resection by postoperative CT scan (P = .15), and frontal lobe tumors (P = .17) tended to survive longer following reoperation. The size of the tumor at the time of recurrence did not correlate with survival following reoperation. Patients with a small amount of peritumoral edema at the time of recurrence tended to survive longer, but the effect was small (P = .16). Prognosis following reoperation cannot be accurately predicted on the basis of tumor appearance on CT scan.

High-dose edatrexate with oral leucovorin rescue: a phase I and clinical pharmacological study in adults with advanced cancer.

Our objective was to determine the maximum tolerated dose and toxicity of i.v. edatrexate with p.o. leucovorin. Thirty-one adults with advanced solid tumors received edatrexate as a 2-h infusion, once a week for 3 weeks, recycled every 28 days. p.o. leucovorin (10 mg/m2, every 6 h for 10 doses) began 24 h later. All had urinary alkalinization and p.o. hydration. Nine dosage levels ranging from 120 to 3750 mg/m2 were explored. Fatigue, epistaxis, nausea/emesis, mucositis, rash, myalgias, leukopenia, thrombocytopenia, and transient elevations of serum aspartate transferase were observed. Leukoencephalopathy with clinical manifestations occurred in two patients (one had prior cranial irradiation). Pharmacokinetic studies carried out at the 120- and 1080-mg/m2 dose levels revealed no significant difference in the elimination half-life at the two dose levels studied and no significant intrapatient variability between day 1 and day 8 edatrexate administration. Serum edatrexate levels measured using a dihydrofolate reductase inhibition assay correlated with those by high-performance liquid chromatography. Three major and two minor antitumor responses occurred. The maximum tolerated dose was 3750 mg/m2, with grade 3 or 4 leukopenia (one patient), stomatitis (one patient), and leukoencephalopathy (one patient). Because of the occurrence of leukoencephalopathy, further study of high-dose edatrexate with leucovorin rescue is not recommended.

The effect of cirrhosis on the steady-state pharmacokinetics of oral ciprofloxacin.

The pharmacokinetics of ciprofloxacin, a carboxyquinolone, was studied after oral administration of the drug to seven patients with biopsy-proved cirrhosis and to seven healthy volunteers. Serum concentrations of ciprofloxacin and its three metabolites--desethylene ciprofloxacin (M1), sulfociprofloxacin (M2), and oxociprofloxacin (M3)--were measured by an HPLC procedure. The pharmacokinetic parameters for ciprofloxacin were not significantly altered in cirrhotic patients. The elimination half-life (t 1/2) and the area under the serum concentration versus time curve (AUC) were, respectively, 3.71 hours and 16.18 microgram.ml-1.hr-1 in the normal subjects and 3.47 hours and 18.38 micrograms.ml-1.hr-1 in patients with cirrhosis. The formation of oxociprofloxacin was reduced by approximately one half in the cirrhotic subjects, as the Cmax was 0.29 micrograms/ml in normal subjects versus 0.14 micrograms/ml in cirrhotic patients and the mean AUC(0-t) was 1.54 micrograms.ml-1.hr-1 in normal subjects versus 0.70 micrograms.ml-1.hr-1 in cirrhotic patients. However, there appeared to be no significant difference between groups with respect to desethylene ciprofloxacin and sulfociprofloxacin. Therefore it appears from this study that no dosage adjustment is required in patients with hepatic cirrhosis.

Effects of aluminum and magnesium antacids and ranitidine on the absorption of ciprofloxacin.

The effect of an antacid (Maalox) and ranitidine administration on the absorption of ciprofloxacin was evaluated in healthy male volunteers who were enrolled in three separate studies. Each study was designed at a three- or four-period crossover and included the administration of 750 mg ciprofloxacin alone as a control treatment. Treatments that were evaluated included the administration of ciprofloxacin 5 to 10 minutes, 2 hours, 4 hours, and 6 hours after a single 30 ml dose of antacid; the administration of antacid 2 hours after ciprofloxacin was given; and the administration of ciprofloxacin 2 hours after a 200 mg ranitidine tablet. Administration of antacid within 4 hours before ciprofloxacin dose resulted in a significant decrease in ciprofloxacin absorption (p less than 0.05). Percentages of relative bioavailability compared with control values were 15.1%, 23.2%, and 70% for the 5 to 10 minute, 2 hour, and 4 hour antacid pretreatments, respectively. Administration of antacid 6 hours before or 2 hours after the ciprofloxacin dose did not affect absorption. Ranitidine did not alter ciprofloxacin absorption. Antacids that contain magnesium and aluminum salts may reduce the absorption of ciprofloxacin. The extent of this interaction appears to increase as the time between administration of the two drugs decreases. Ranitidine is suggested as an alternative to antacids for patients receiving treatment with ciprofloxacin.

Distribution of brain metastases.

The number and site of brain metastases were identified on the computed tomographic scans of 288 patients. There was one brain metastasis in 49%, two in 21%, three in 13%, four in 6%, and five or more in 11% of scans. In patients with one metastasis, the posterior fossa was involved in 50% of patients when the primary tumor was pelvic (prostate or uterus) or gastrointestinal, but it was involved in only 10% of patients with other primary tumors. Hemispheral metastases preferred the anatomic "watershed areas" (29% of the brain surface contained 37% of the metastases), indicating that tumoral microemboli tend to lodge in the capillaries of the distal parts of the superficial arteries. The charts of 134 patients with brain metastases from a primary tumor originating outside the lung revealed that the incidence of lung and spine metastases was the same, whether the primary tumor was pelvic or gastrointestinal or from another site. These data suggest that the high incidence of subtentorial lesions in patients with pelvic and gastrointestinal primary tumors cannot be explained by arterial embolization alone, and that this peculiar distribution is probably not explained by seeding of the brain through Batson's plexus.

Low-grade oligodendroglioma responds to chemotherapy.

We administered chemotherapy in standard and intensified formulations of procarbazine, lomustine (CCNU), and vincristine to nine symptomatic patients with low-grade oligodendroglioma. Eight patients were treated with chemotherapy at presentation and one was treated for a recurrence after radiotherapy had failed. All patients improved by clinical or MRI criteria, or both. No patient deteriorated while in therapy and the responses were sustained without radiotherapy for a median of 35 months (range, 22-45) in all surviving patients treated at presentation. Chemotherapy was well tolerated; all patients developed myelosuppression, but only those receiving the intensified regimen required dose reduction or premature discontinuation of treatment. As with recurrent and anaplastic oligodendroglioma, low-grade oligodendroglioma responds to chemotherapy.

CT of the brachial plexus in patients with cancer.

To assess the usefulness of CT, we reviewed 51 patients with clinically diagnosed brachial plexopathy who were seen between 1977 and 1981. The established etiology was metastatic tumor in 46 and radiation fibrosis in 5. CT was abnormal in 89% of tumor patients. Myelography, bone scan, and plain cervical spine radiographs were less useful. In four of five patients with radiation fibrosis, CT showed distortion of normal tissue planes without a discrete mass, but was not always distinguishable from tumor infiltration. CT of the brachial plexus provides the best two-dimensional view of tumor infiltration and detects bony changes earlier than standard radiographs. CT is a useful guide for surgical exploration of the brachial plexus, but does not differentiate tumor infiltration from radiation fibrosis.

Primary CNS lymphoma: combined treatment with chemotherapy and radiotherapy.

Primary central nervous system lymphoma (PCNSL), an uncommon tumor, is occurring with increasing frequency. Conventional therapy with corticosteroids and cranial radiotherapy (RT) usually gives a dramatic initial response, but median survival is only 10 to 18 months. Chemotherapy is more successful in comparable systemic lymphoma and has been employed for PCNSL at relapse, causing remission but not cure. Between June 1985 and June 1988, we prospectively staged 32 patients with PCNSL at Memorial Sloan-Kettering Cancer Center and treated 28 on a new protocol that combined chemotherapy and radiotherapy at diagnosis. None had occult systemic lymphoma, but 19% had ocular and 69% had definite or probable leptomeningeal lymphoma. There were no complications in 19 stereotactic biopsies, but 4/10 patients who had a complete resection suffered a severe postoperative deficit. Four patients received RT alone, and 28 received chemotherapy and cranial RT, 17 of whom (group A) received a combination regimen using pre-RT systemic (1 g/m2) and intra-Ommaya methotrexate (MTX), 4,000 cGy whole-brain RT with a 1,440 cGy boost, and 2 courses of post-RT high-dose cytosine arabinoside; 5 other patients received an identical regimen but with a decreased dose of MTX (200 mg/m2). Sixty-three percent of assessable patients had a response to MTX independent of corticosteroid and prior to RT. Eighteen of 26 (69%) assessable patients who received combined therapy are alive with a median follow-up of 25.4 months. Twelve of 16 (75%) assessable group A patients are alive in the same period. Chemotherapy-related toxicity was minimal, and no late toxicities have occurred to date.(ABSTRACT TRUNCATED AT 250 WORDS)

MRI changes in intracranial hypotension.

We report seven patients with the syndrome of intracranial hypotension who were referred to Memorial Sloan-Kettering, primarily because of suspicion of meningeal tumor or infection raised by the finding of meningeal enhancement on MRI. In three patients, symptoms occurred after lumbar puncture; in four, there was no clear precipitating event. Lumbar puncture after MRI in six patients revealed low CSF pressure (six patients) and pleocytosis or high protein, or both (four patients). Three patients had subdural effusions. Six patients had measurable descent of the brain on midsagittal images. Postural headache resolved in all seven patients, six of whom had follow-up MRIs. Meningeal enhancement resolved or diminished in all six. Subdural effusions resolved spontaneously in two and were evacuated (but were not under pressure) in one. Downward brain displacement improved or resolved in all patients. The clinical syndrome and MRI abnormalities generally resolve on their own. An extensive workup is not helpful and may be misleading. Patients should be treated symptomatically.

Balancing service and education: improving internal medicine residencies in the managed care era.

BACKGROUND: Internal medicine training programs must adapt to health care systems faced with balancing the competitive priorities of patient-care responsibilities and educational needs. OBJECTIVE: To evaluated the effects of a major organizational change on the inpatient service of an internal medicine residency program in a vertically integrated health system. METHODS: We changed the structure of our program from a system in which the hospitalized patients' primary physicians were responsible for daily inpatient management, while teaching was assigned to a defined teaching rounder, to a method in which the rounding attending was responsible for both teaching and patient care. Measurements before and after the change in the rounding system included: the McGill University clinical tutor evaluations, time-motion observations of house staff, patient satisfaction surveys, average length of stay data, and physician focus groups to assess physician satisfaction. RESULTS: The rounding attendings consistently received excellent to superior ratings by the house staff both before and after the implemented change. Compared to time-motion observations performed before the change, observations recorded after the change suggested that a greater percent of house staff time was spent on educational activities. The responses of patient satisfaction surveys indicated that the perception of quality of care remained high after the system change. Lastly, the average length of stay for patients on the general internal medicine and subspecialty services was reduced from 7.6 days before the change to 6.6 days after the change, a difference of 0.92 day (95% confidence interval 1.3 to 0.6, P < 0.001). CONCLUSIONS: Through organizational restructuring, it is possible to improve the quality of patient care and improving the efficiency of patient-care management.

Patterns of failure following treatment for glioblastoma multiforme and anaplastic astrocytoma.

Recurrence patterns of glioblastoma multiforme (25) and anaplastic astrocytoma (9) were studied using CT scans of 34 patients who received all or a portion of their surgical treatment at Memorial Sloan-Kettering Cancer Center from January 1983 through February 1987. Thirty-two patients presented with unifocal tumors and two with multifocal tumors. All patients received radiation therapy following initial surgery. Eighteen patients who underwent re-operation following CT evidence of recurrence had histologic verification of recurrent tumor; sixteen patients had radiographic evidence of recurrence only. Seventy-eight percent (25/32) of unifocal tumors recurred within 2.0 cm of the pre-surgical, initial tumor margin, defined as the enhancing edge of the tumor on CT scan. Fifty-six percent (18/32) of tumors recurred within 1.0 cm of the initial tumor margin. Tumors for which a gross total resection was accomplished tended to recur closer to the initial tumor margin than did subtotally resected tumors (p greater than 0.1). Extensive pre-operative edema was associated with a decreased distance between initial and recurrent tumor margins. Large tumors were generally not more likely to recur further from the initial tumor margin than were smaller tumors. No unifocal tumor recurred as a multifocal tumor. Only one tumor (initially near the midline) recurred in the contralateral hemisphere. The findings support the use of partial brain irradiation for post-operative treatment of glioblastoma multiforme and anaplastic astrocytomas, and may help to determine the most appropriate treatment volume for interstitial irradiation.

Effectiveness of sotalol for atrial flutter in children after surgery for congenital heart disease.

This study describes the efficacy of oral sotalol in the treatment and prevention of atrial flutter in children after surgery for congenital heart disease. In 11 of 13 children (85%), conversion to sinus rhythm was achieved, and in 8 of 11 within 24 hours.

Value and pitfalls of the lateral lung scan.

Two hundred eighty-one of 443 lung scans composed of anterior, posterior, and lateral projections (done in our hospital) demonstrated defects. In 3.9 percent of them (11 cases), the defects were delineated in the lateral views only, while in 29.2 percent (82 cases), the lateral views either outlined additional defects not appreciated on the straight views, or showed more extensive lung involvement. In the majority of instances, 56.6 percent (159 cases), the lateral views showed comparable findings and also tended to segmentally localize the defects better. However, in 10.3 percent (29 cases), defects present on the straight projections were not detected on the lateral views. Various causes that could give rise to artefactural abnormalities in the lateral lung scan and therefore inhibit its proper interpretation, are reviewed and discussed. Despite these problems, the lateral may be the only view to demonstrate abnormalities and, in fact, frequently provides additional useful information.

Comparison of longevity, pacing, and sensing characteristics of steroid-eluting epicardial versus conventional endocardial pacing leads in children.

OBJECTIVE: Because of either cardiac anatomy or small size, pacing in children often occurs by means of epicardial leads. The disadvantage of epicardial leads is the shorter longevity of these leads compared with endocardial leads. During short-term follow-up, improved stimulation thresholds were found for the newer steroid-eluting epicardial leads. The longevity of these leads may be better than that of conventional epicardial leads. An improved longevity of epicardial leads may influence the choice to either epicardial or endocardial pacing in children. METHODS: We studied the longevity and the pacing and sensing characteristics of 33 steroid-eluting epicardial pacing leads (group I, 15 atrial, 18 ventricular) implanted between November 1991 and October 1996 in 20 children with a mean age of 7.6 +/- 6.5 years (mean +/- SD), and 29 endocardial pacing leads (group II, 15 atrial, 14 ventricular) implanted during the same period in 21 children with a mean age of 11.7 +/- 4.7 years. RESULTS: The mean follow-up in group I was 2.9 +/- 1.6 years and in group II 3.1 +/- 1.7 years (P =.61). The 2-year survival of the leads in group I was 91% +/- 5% and in group II 86% +/- 7% (P =.97). Lead failure occurred in both groups in 4 leads (P =.85). Chronic stimulation and sensing thresholds were similar. CONCLUSIONS: Steroid-eluting epicardial leads have the same longevity as the conventional endocardial leads. Pacing and sensing thresholds were similar and did not change during follow-up. Therefore steroid-eluting epicardial pacing leads are a good alternative for endocardial leads in small children and in children with congenital heart disease.

Metabolic responses to moderate exercise in lambs with aortopulmonary shunts.

In a previous study we found, after an overnight fast of 18 hours, a lower arterial glucose concentration and a depressed glycogenolysis in lambs with aortopulmonary left-to-right shunts. During exercise, glucose and free fatty acids (FFA) concentrations normally increase. The aim of this study was to investigate whether the shunt lambs could compensate for a depressed glycogenolysis by increasing gluconeogenesis and by increasing levels of blood substrates such as FFA and glycerol during exercise. Therefore, we investigated glucose kinetics, with [U-(13)C]glucose, in five 7-week-old shunt and 7 control lambs of a similar age, at rest and during moderate exercise (treadmill; 50% of VO(2) peak). The glucose production rate and the rate of disappearance of glucose were lower in shunt than in control lambs, both at rest and during exercise. We found no difference in metabolic clearance rate of glucose, glucose recycling, or gluconeogenesis between both groups of lambs. Glycogenolysis was at rest lower in shunt than in control lambs and tended to be lower during exercise. The arterial concentrations of pyruvate, lactate, FFA, and total and free glycerol increased during exercise in both groups of lambs. In conclusion, shunt lambs have lower arterial glucose concentrations than control lambs, both at rest and during moderate exercise. This was due to a lower glucose production rate, in particular a lower glycogenolysis. In addition, the reduced glycogenolysis rate was not offset by an increase in gluconeogenesis nor by an increase in other substrates that can be utilized by working muscles.

Lower arterial glucose concentrations in lambs with aortopulmonary shunts after an 18-hour fast.

Spontaneously occurring hypoglycemia has been described in children with severe acute congestive heart failure. Hypoglycemia may be the result of an increase in glucose utilization in tissues, a decrease in glucose production, or a decrease in the dietary intake of nutrients. To determine whether hypoglycemia may also occur in congenital heart disease with volume overloading, we investigated glucose metabolism during and after an 18-hour fast in nine lambs with an aortopulmonary left-to-right shunt and nine control lambs. Plasma levels of hormones involved in the endocrine control of glucose metabolism were determined. The glucose production rate (rate of appearance [Ra]) was studied using [U-13C]glucose. Gluconeogenesis through the Cori cycle was estimated by measuring glucose 13C recycling. The arterial glucose concentration (3,409 +/- 104 v 4,338 +/- 172 micromol/L, P < .001) and Ra of glucose (16.97 +/- 0.89 v 25.49 +/- 4.28 micromol x min(-1) x kg(-1), P < .05) were lower in shunt versus control lambs. There were no differences in hormone levels between control and shunt lambs. Fractional glucose 13C recycling via the Cori cycle (6.9% +/- 2.8% v 7.1% +/- 2.5%) and gluconeogenesis from pyruvate and lactate (1.24 +/- 0.58 v 1.95 +/- 0.67 micromol x min(-1) x kg(-1)) were similar in both groups of lambs. The sum of glycogenolysis and gluconeogenesis from precursors other than pyruvate and lactate was lower in shunt versus control lambs (15.73 +/- 1.07 v 23.54 +/- 4.27 micromol x min(-1) x kg(-1), P < .05). In conclusion, after an 18-hour fast, the arterial glucose concentration is lower in lambs with aortopulmonary shunts. This lower glucose concentration is associated with a decreased glucose production rate. In shunt lambs, glycogenolysis is decreased, while there is no difference in gluconeogenesis or hormonal control.