Randomised phase II trial of irinotecan plus S-1 in patients with gemcitabine-refractory pancreatic cancer.

BACKGROUND: We aimed to compare the efficacy and safety of irinotecan/S-1 (IRIS) therapy with S-1 monotherapy in patients with gemcitabine-refractory pancreatic cancer. METHODS: Patients were treated with oral S-1 (80-120 mg for 14 days every 4 weeks) plus intravenous irinotecan (100 mg m-2 on days 1 and 15 every 4 weeks; IRIS group) or oral S-1 group (80-120 mg daily for 28 days every 6 weeks). The primary endpoint was progression-free survival (PFS). RESULTS: Of 137 patients enrolled, 127 were eligible for efficacy. The median PFS in the IRIS group and S-1 monotherapy group were 3.5 and 1.9 months, respectively (hazard ratio (HR)=0.77; 95% confidence interval (CI), 0.53-1.11; P=0.18), while the median overall survival (OS) were 6.8 and 5.8 months, respectively (HR=0.75; 95% CI, 0.51-1.09; P=0.13). Response rate was significantly higher in the IRIS group than in the S-1 monotherapy group (18.3% vs 6.0%, P=0.03). Grade 3 or higher neutropenia and anorexia occurred more frequently in the IRIS group. CONCLUSIONS: There was a trend for better PFS and OS in the IRIS group that could be a treatment arm in the clinical trials for gemcitabine-refractory pancreatic cancer.

Polymorphism in promoter region of growth hormone receptor is associated with potential production capacity of insulin-like growth factor-1 in pre-pubertal Holstein heifers.

Insulin-like growth factor-1 (IGF-1) is one of the important factors for growth, milk production and reproductive functions and mainly released from the liver in response to growth hormone (GH) via GH receptor (GHR) in cattle. Recently, some single nucleotide polymorphisms (SNPs) were identified in the bovine GHR gene. Some GHR-SNPs were shown to be related to plasma IGF-1 concentration in cattle. Hence, the capacity to IGF-1 production in the liver might be affected by GHR-SNP and associated with performance in the future. This study examined whether GHR-SNP is associated with IGF-1 production in the liver of pre-pubertal heifers. In 71 Holstein calves, blood samples for genomic DNA extraction were obtained immediately after birth. To genotype the GHR-SNPs in the promoter region, polymerase chain reaction (PCR) products were digested with restriction enzyme NsiI (cutting sites: AA, AG and GG). All heifers at 4 months of age were intramuscularly injected with 0.4 mg oestradiol benzoate. Blood samples were obtained from the jugular vein just before (0 h) and 24 h after injection. The number of AA, AG and GG at the NsiI site was 0, 17 and 54 respectively. In AG and GG, plasma GH concentrations were higher pre-injection than 24 h post-injection (p < 0.01). Moreover, plasma GH concentrations in AG post-injection were higher than in GG (p < 0.05). In contrast, the GG genotype exhibited higher plasma IGF-1 concentrations in pre-injection than post-injection (p < 0.01), although oestradiol did not change IGF-1 concentration in the AG genotype. We conclude that the GG polymorphism in the promoter region of GHR is associated with a higher potential capacity of IGF-1 production in the liver of cattle.

Hepatic arterial infusion of mitomycin C with degradable starch microspheres for unresectable intrahepatic cholangiocarcinoma.

AIMS: With no effective chemotherapy, the prognosis of unresectable intrahepatic cholangiocarcinoma is extremely poor. Hepatic arterial infusion of mitomycin C with degradable starch microspheres has been reported to be an effective treatment for unresectable liver metastasis. We retrospectively evaluated the efficacy and safety of this chemotherapy for treating unresectable intrahepatic cholangiocarcinoma. MATERIALS AND METHODS: Hepatic arterial infusion chemotherapy through an implanted port system was carried out in 20 patients with unresectable intrahepatic cholangiocarcinoma. Degradable starch microspheres mixed with mitomycin C and contrast media were injected until either embolisation of the hepatic artery or influx to the gastroduodenal system was confirmed. This treatment was repeated weekly. RESULTS: Hepatic arterial infusion chemotherapy was carried out 204 times. The response rate was 50.0%. Twelve patients experienced transient epigastralgia and four experienced gastroduodenal ulcer. The time to progression was 8.3 months and the median survival time was 14.1 months. CONCLUSIONS: This chemotherapy was effective and feasible for patients with unresectable intrahepatic cholangiocarcinoma. Further study with a larger number of patients is warranted.

[Successful treatment for descending necrotizing mediastinitis; report of a case].

A case of a 55-year-old man with descending necrotizing mediastinitis (DNM) after a tooth removal was reported. Chest computed tomography (CT) showed a fluid collection in the right thorax, in the cervical region and in the mediastinum. The patient underwent cervical drainage and thoracoscopic pleural dissective drainage. The cervical and right anterior thoracic drain was removed on the 6th day and posterior drain was removed on the 8th day after the operation. The patient was discharged on the postoperative day 13, and showed no recurrence.

Phase I/II study of docetaxel and S-1 in patients with advanced gastric cancer.

The aims of this phase I/II study of docetaxel and S-1 were to determine the dose-limiting toxicity (DLT), maximum-tolerated dose (MTD), and recommended dose (RD) in the phase I part and to explore the tumour response, survival and safety in the phase II part. Patients with histologically- or cytologically confirmed unresectable or recurrent gastric cancer were eligible. Treatment consisted of intravenous docetaxel on day 1 (starting dose 50 mg m(-2)) and oral S-1 at a fixed dose of 40 mg m(-2) twice daily on days 1-14, every 4 weeks up to six cycles. Nine patients took part in the phase I portion of the study. The MTD of docetaxel was determined to be 50 mg m(-2), with the DLTs of grade 3 infection associated with grade 3 neutropenia and grade 4 neutropenia during S-1 administration. The RD of docetaxel was 40 mg m(-2) in combination with S-1 40 mg m(-2) b.i.d. The efficacy and safety of this regimen was therefore assessed in 46 patients with at least one measurable lesion. The overall response rate and estimated median overall survival were 46% (95% CI, 31-61%) and 14.0 months (8.3-17.3 months), respectively. The most common grade 3/4 toxicity was neutropenia (67% of patients), which was predictable and manageable. This regimen showed promising activity with moderate toxicities in advanced gastric cancer.

[Modified bentall operation using composite graft without resection of aortic valve].

A 27-year-old male whose diagnoses were aortic dissection (Stanford A), aortic regurgitation, annulo-aortic ectasia, and Marfan syndrome underwent modified Bentall operation using composite graft and total arch replacement. Modification of proximal suture without resection of aortic valve like intravalvular implantation might have resulted in good recovery without blood transfusion. Another 63-year-old male who suffered from spontaneous aortic rupture with aortic regurgitation also underwent modified Bentall operation in the similar manner as the first case with good result. Spontaneous aortic rupture reported here is a rare case, and operation is thought to be prerequisite for the patient who suffers from this disease to survive.

[A report of three surgical cases in a family of Marfan syndrome].

A family of 3 patients with Marfan syndrome was reported. All of them had surgical interventions in cardiovascular disorders such as DeBakey type I, III aortic dissection and thoracoabdominal aortic aneurysm. In 2 patients, multiple surgical treatments were performed for aneurysmal dilatation of the distal false lumen or another lesions of the treated aorta. Since cardiovascular lesions of Marfan syndrome are systemic and progressive, the postoperative long term follow-up, including systemic evaluation of the arterial system, is essential to detect the latent cardiovascular complications. Careful examining the family with Marfan syndrome is necessary to discover any cardiovascular abnormalities in these people early.

Myocardial protection of the pressure overload hypertrophied heart in human cardiac surgery by acceleration of anaerobic glycolysis.

BACKGROUND: Because of the decreased tolerance to ischemia and increased reperfusion injury in hypertrophied myocardium, myocardial hypertrophy is a well known risk factor for cardiac surgery. We have previously demonstrated in a left ventricular hypertrophy (LVH) model that a highly buffered cardioplegic solution (HBS) that provided glucose as a substrate and promoted anaerobic glycolysis during ischemia afforded superior myocardial protection when compared to standard formulations. And we reported the superiority of this cardioplegia in human cardiac surgery. METHODS: In this study, 16 patients with aortic stenosis (AS) and LVH receiving HBS were reviewed and compared to another patient group with AS and LVH who received either cold blood cardioplegia (CBC; n=5) or glucose insulin potassium (GIK; n=6). RESULTS: Postoperative cardiac index was better in the HBS group than the other two groups with similar or lower catecholamine. CK-MB was lower in HBS group than GIK group, but this was not significant. Only one DC cardioversion was required in the HBS group, whereas 2 DC in the CBC group and total 7 DC in the GIK group. CONCLUSIONS: We found that histidine buffered cardioplegic solution provided comparable or better pump performance after surgery with relatively lower inotropic requirement, less DC cardioversion and homologous blood requirements for left ventricular hypertrophied heart associated with aortic stenosis.

A novel mutation in glial fibrillary acidic protein gene in a patient with Alexander disease.

Alexander disease is a rare, progressive, leukoencephalopathy whose hallmark is the widespread accumulation of Rosenthal fibers. The most common form affects infants and young children, and is characterized by progressive failure of central myelination, usually leading to death before adulthood. Definitive diagnosis of Alexander disease has required biopsy or autopsy to demonstrate the presence of Rosenthal fibers. However, missense mutations in the coding region of the glial fibrillary acidic protein (GFAP) gene have recently been associated with a high percentage of pathologically proven cases. Here we report that a 10-year-old Japanese patient who showed clinical signs of Alexander disease is heterozygous for a C to T transition in which predicts a novel A244V amino acid substitution in the conserved 2A alpha-helix domain of GFAP. The nucleotide change was not found in 65 normal individuals (130 alleles). These results provide further support for a causative role for GFAP mutations in Alexander disease, and suggest DNA sequencing as an alternative diagnostic to biopsy.

Prediction of safe duration of hypothermic circulatory arrest by near-infrared spectroscopy.

OBJECTIVE: Hypothermic circulatory arrest is widely used for adults with aortic arch disease as well as for children with congenital heart disease. At present, no method exists for monitoring safe duration of circulatory arrest. Near-infrared spectroscopy is a new technique for noninvasive monitoring of cerebral oxygenation and energy state. In the current study, the relationship between near-infrared spectroscopy data and neurologic outcome was evaluated in a survival piglet model with hypothermic circulatory arrest. METHODS: Thirty-six piglets (9.36 +/- 0.16 kg) underwent circulatory arrest under varying conditions with continuous monitoring by near-infrared spectroscopy (temperature 15 degrees C or 25 degrees C, hematocrit value 20% or 30%, circulatory arrest time 60, 80, or 100 minutes). Each setting included 3 animals. Neurologic recovery was evaluated daily by neurologic deficit score and overall performance category. Brain was fixed in situ on postoperative day 4 and examined by histologic score. RESULTS: Oxygenated hemoglobin signal declined to a plateau (nadir) during circulatory arrest. Time to nadir was significantly shorter with lower hematocrit value (P <.001) and higher temperature (P <.01). Duration from reaching nadir until reperfusion ("oxygenated hemoglobin signal nadir time") was significantly related to histologic score (r (s) = 0.826), neurologic deficit score (r (s) = 0.717 on postoperative day 1; 0.716 on postoperative day 4), and overall performance category (r (s) = 0.642 on postoperative day 1; 0.702 on postoperative day 4) (P <.001). All animals in which oxygenated hemoglobin signal nadir time was less than 25 minutes were free of behavioral or histologic evidence of brain injury. CONCLUSION: Oxygenated hemoglobin signal nadir time determined by near-infrared spectroscopy monitoring is a useful predictor of safe duration of circulatory arrest. Safe duration of hypothermic circulatory arrest is strongly influenced by perfusate hematocrit value and temperature during circulatory arrest.

Identification of endogenous ouabain in culture supernatant of PC12 cells.

OBJECTIVE: Ouabain-like factor (OLF), assayed as ouabain-like immunoreactivity (OLI), is thought to represent an endogenous digitalis-like factor. We found increased plasma OLI during the surgical removal of a pheochromocytoma. The elution volume of the OLI extracted from plasma and the pheochromocytoma tissue was the same as that for authentic ouabain, using reverse phase high-performance liquid chromatography. The present study was performed to characterize OLF from the culture supernatant of a rat pheochromocytoma cell line, PC12 cells. DESIGN: OLI from culture supernatant and chromatographic fractions were assayed by a sensitive enzyme-linked immunosorbent assay for ouabain. PC12 cells, subcultured in RPMI 1640 with 10% horse serum and 5% fetal bovine serum, were washed, and then cultured in Iscove's modified Dulbecco's medium (Life Technologies, Rockville, Maryland, USA) with 0.4% bovine serum albumin (without serum). Progesterone was added to augment the production or secretion of OLI. The conditioned medium was acidified to dissociate the binding protein, and OLI was purified by five steps of octadecylsilane (ODS) column chromatography. The structural identity of this OLI was determined by liquid chromatography and mass spectrometry (LC/MS). RESULTS: OLI in the culture medium increased after addition of progesterone in a dose-dependent manner. The concentration in the culture medium was approximately double of that in homogenized PC12 cells. After five rounds of ODS column chromatography, approximately 100 ng of OLI was purified from 21 of culture supernatant, without fetal calf serum, in the presence of progesterone. The molecular size of purified OLI was found to be identical to authentic ouabain, based on analysis by LC/ MS. CONCLUSION: Mammalian cells originating from a rat pheochromocytoma cell line were found to produce and/or secrete OLF by the addition of progesterone.

Improving glucose metabolism and/or sarcoplasmic reticulum Ca2+-ATPase function is warranted for immature pressure overload hypertrophied myocardium.

The cellular mechanisms of abnormal calcium regulation and excitation-contraction coupling in relation to glucose metabolism in the hypertrophied heart are not well understood. The present study evaluated the myocardial mechanics of 6-7-week-old pressure overload hypertrophied rabbit hearts in response to dobutamine by (1) serial echocardiograms in vivo and (2) isolated Langendorff perfusion. Cytosolic Ca2+([Ca2+]i) and sarcoplasmic reticulum Ca2+-ATPase (SERCA2) expression were measured by fluorescence spectroscopy and Western immunoblotting, respectively. The effect of glycolytic inhibition by 2-deoxy-D-glucose +/- pyruvate was also evaluated. Both systolic and diastolic [Ca2+]i tended to be higher and diastolic calcium removal (tauCa) significantly slower in the hypertrophied heart. The myocardial response to dobutamine was blunted and dobutamine insignificantly improved tauCa. The SERCA2 protein level was higher in early hypertrophy, but was significantly reduced by 6 weeks of age, with progressive contractile failure. Inhibition of glycolysis or SERCA2 caused an increase in [Ca2+]i as well as a slower tauCa. Pyruvate completely preserved myocardial function and [Ca2+]i handling during glycolytic inhibition. It was concluded that in this model of advanced pressure overload hypertrophy, contractile failure and inotrope insensitivity are associated with increased [Ca2+]i, slower tauCa and reduced sensitivity of the contractile proteins to Ca2+. These changes occur in association with downregulation of the SERCA2, probably caused by impaired glucose metabolism.

Exhaled nitric oxide--is it really a good marker of airway inflammation in bronchial asthma?

BACKGROUND: The concentration of exhaled nitric oxide ([NO]) has been reported to reflect the inflammatory process of airways in patients with bronchial asthma, particularly when they are steroid naive. However, it is not fully understood whether it equally reflects the degree of airway inflammation in patients receiving inhaled corticosteroids, but whose symptoms are not necessarily well controlled. OBJECTIVE: To examine whether the exhaled [NO] really reflects airway inflammation in patients with bronchial asthma, regardless of treatment with inhaled steroids. METHODS: Exhaled [NO] was measured in patients with bronchial asthma (43 steroid treated and 32 steroid naive), chronic obstructive pulmonary disease (COPD) (n = 36), bronchiectasis (n = 10) and in control subjects (n = 26). We examined in each asthmatic group whether the exhaled [NO] correlated with parameters reflecting airway inflammation. RESULTS: Exhaled [NO] was significantly correlated with symptom score, clinical severity, circulating eosinophil count, and the percentage of eosinophils in induced sputum in the steroid-naive asthmatics, but not in the steroid-treated asthmatics, although airway inflammation in this group was not well controlled, as evidenced by clinical symptoms and the higher percentage of eosinophils in induced sputum. Exhaled [NO] from the patients with COPD (6.2 +/- 0. 7 ppb) or bronchiectasis (5.4 +/- 1.3 ppb) was not significantly increased compared with the controls (6.0 +/- 1.0 ppb), and was significantly lower than in the asthmatic patients as a whole (19.0 +/- 2.0 ppb). CONCLUSIONS: Although exhaled [NO] is a useful marker of airway inflammation for differential diagnosis and evaluation of severity in steroid-naive patients with bronchial asthma, it may not be as useful in steroid-treated patients.

Serum KL-6 concentrations in dairy farmers.

STUDY OBJECTIVES: Serum KL-6 (Krebs von den Lungen-6) has been recognized to be a marker for the activity of diffuse interstitial lung diseases. The purpose of the study is to evaluate serum KL-6 measurement as a marker for farmer's lung disease (FLD). DESIGN: A cross-sectional survey of a cohort of dairy farmers. Retrospective measurement of KL-6 stored serum samples from those dairy farmers previously screened for FLD. SETTING: University hospital screening project for FLD within a dairy-farming community in Japan. PARTICIPANTS: Four hundred seventy-two dairy farmers were invited to attend a local clinic. MEASUREMENTS AND RESULTS: We examined serum KL-6 concentrations in 272 farmers. Subjects were classified into three groups: (1) 5 farmers with FLD, (2) 30 farmers with positive serum precipitating antibodies to Saccharopolyspora rectivirgula and/or Thermoactinomyces vulgaris without FLD (Ab(+)), and (3) 237 farmers without these antibodies (Ab(-)). Serum KL-6 concentrations in the FLD group were significantly higher than those in the Ab(+) and the Ab(-) groups (1,263 +/- 288 [SEM], 328 +/- 57, and 207 +/- 6 U/mL, respectively, p < 0.001). Serum KL-6 concentrations in those with FLD were significantly higher than KL-6 concentrations from stored screening samples from the same individual when FLD was not diagnosed (1,263 +/- 288 and 419 +/- 209 U/mL, respectively, p < 0.05). Serum KL-6 concentrations of the Ab(+) group were significantly higher than those of the Ab(-) group (p < 0.001). In the Ab(+) group, farmers with high serum KL-6 concentrations had lower permeability coefficients than farmers with normal serum KL-6 concentrations (p < 0.05). These results may suggest that subclinical FLD can be detected in farmers with high KL-6 concentrations and precipitating antibodies. CONCLUSION: Serum KL-6 concentration can be a useful marker for assessing the activity of FLD and may be able to be used to detect subclinical disease.

Nafamostat mesilate modulates the release of platelet-activating factor during left ventricular assistance with hemofiltration in canine heart failure.

OBJECTIVE: The enhanced generation of various chemical mediators is regarded as one of the mechanisms by which severe heart failure progresses to multiple organ failure. Platelet-activating factor is a phospholipid mediator which plays an important role in inflammatory reactions and circulatory shock. We studied the changes in platelet-activating factor levels in a canine heart failure model treated with a left ventricular assist device and hemofiltration, and assessed the effect of a protease inhibitor, nafamostat mesilate. METHODS: Twenty dogs underwent multiple coronary ligations, and at 2 hours after the ligations they were maintained on left ventricular assist device support with continuous hemofiltration. The animals were divided into two groups: a nafamostat group (n = 10) that received nafamostat mesilate (2 mg/kg/hr), and a control group (n = 10) that received vehicle only. RESULTS: The blood platelet-activating factor level, before coronary ligations, in the control and nafamostat groups was 2.3 +/- 0.4 and 2.0 +/- 0.7 ng/ml, respectively, and the coronary ligations had little effect on the platelet-activating factor. However, after the initiation of left ventricular assist device, the platelet-activating factor in the control group (5.6 +/- 2.2) was significantly higher (p < 0.05) than that in the nafamostat group (1.1 +/- 0.3). Nafamostat administration was also effective in controlling the increase in the blood lactate level. Hemofiltration did not change the platelet-activating factor. CONCLUSIONS: We concluded that platelet-activating factor may play a critical role in the development of severe heart failure with left ventricular assistance, and nafamostat administration is likely to be beneficial in such a critical condition by suppressing the platelet-activating factor level.

Bridged silver(I) complexes of the polycyclic aromatic compounds tetraphenylethylene and 1,1,4,4-tetraphenyl-1,3-butadiene.

For the purpose of investigating the coordination behavior of the sterically congested alkenes and exploring the possibility of cofacial complexation in the polycyclic aromatic system for formation of extended polymeric networks, tetraphenylethylene (tphe) and 1,1,4,4-tetraphenyl-1,3-butadiene (tphb) have been studied with regard to their complexation with a silver(I) ion. The crystal structures of [Ag(tphe)(ClO4)(p-xylene)], [Ag2(tphe)(ClO4)2], [Ag4(tphe)(CF3SO3)4], [Ag2(tphb)(ClO4)2], and [Ag2(tphb)(CF3SO3)2], together with the metal-free ligands tphe and tphb, have been determined by single-crystal X-ray diffraction. The pi-electron-rich cleft in organic components is found to offer a potential site for complexation, which can be utilized to generate an interesting array of organometallic compounds with one- and two-dimensional frameworks.

Increases in plasma ouabainlike immunoreactivity during surgical extirpation of pheochromocytoma.

The ouabainlike factor (OLF) is thought to be an important modulator of salt and water metabolism. Plasma OLF could be derived from the central nervous system and/or the adrenal gland. Since the adrenal medulla is of neural origin, the cytology of pheochromocytoma of adrenomedullary origin resembles that of neuronal cells. Ouabainlike immunoreactivity (OLI) is, in fact, present in the adrenal medulla as shown by immunohistochemistry. The plasma levels of catecholamines and OLI were significantly elevated during surgical extirpation of pheochromocytoma in this case. To clarify the origin of circulating OLI in a patient with pheochromocytoma, the relationship between plasma OLI and catecholamines during adrenalectomy was investigated. Plasma catecholamine levels exceeded the normal reference interval, and plasma OLI was positively correlated with the patient's plasma level of norepinephrine. The peak level during operation was about 10 times higher than the baseline level. Both levels reached a maximum when the tumor was mechanically pressed, and then gradually decreased thereafter. The level of OLI in the tumor was higher than that of the normal adrenal cortex. When OLI in the tumor was characterized by reversed-phase high-performance liquid chromatography, the retention time of OLI corresponded with that of authentic ouabain. These results suggest that the circulating OLI in this patients was derived mainly from the pheochromocytoma of adrenomedullary origin.

[Histidine buffered cardioplegic solution (HBS) provides effective myocardial preservation with wider safety margin in patients with prolonged ischemia].

Increasingly complex techniques of cardiac surgery often require prolonged myocardial ischemia. We previously reported a better myocardial preservation with histidine containing cardioplegia (HBS) in human open heart surgery. To see a safety margin of this cardioplegia for prolonged myocardial preservation, this study was retrospectively done. One hundred twenty-six patients received either intermittent multidose (20-30 minute) cold blood cardioplegia (CBC) plus topical cooling (aotric cross clamp time (ACC) < 120 minutes, n = 63) or HBS (n = 63). HBS group was divided into two groups with either short ACC (< or = 120 minutes, HBS-S, n = 46) or long ACC (> 120 minutes, HBS-L, n = 17). Cardiac index (C.I.) and dopamin/dobutamine requirement were measured 3, 6, and 12 hours post-bypass. Incidence of homologous blood transfusion was also studied. There was two deaths due to LOS in HBS-S group; four patients in HBS group required 5 DC cardioversion, whereas six patients required a total of 12 DC cardioversion in CBC group. Functional recovery were significantly better with significantly lower inotropic requirements in HBS-S group than CBC group and HBS-L group. Although preoperative ejection fraction and C.I. were significantly lower in HBS-L group, post-operative cardiac function and inotropic requirements in HBS-L was comparable to that seen in CBC group. We conclude that the highly buffered histidine crystalloid cardioplegia solution provides effective myocardial preservation with a wider safety margin for prolonged myocardial preservation in open heart surgery.

Altered sympathetic and vagal modulations of the cardiovascular system in patients with pheochromocytoma: their relations to orthostatic hypotension.

To examine sympathetic and vagal cardiovascular regulatory mechanisms in the pathogenesis of orthostatic hypotension in pheochromocytoma, we continuously monitored blood pressure (Finapres) and RR interval (electrocardiogram) in supine and standing positions in 12 patients with pheochromocytoma, 43 patients with essential hypertension, and 30 normotensive subjects. Mayer wave power spectrum of systolic blood pressure variability (approximately 0.1 Hz) and respiratory power spectrum of the RR interval variability (approximately 0.25 Hz) were taken as measures of sympathetic vascular and cardiac vagal modulations, respectively. Systolic blood pressure decreased more upon standing in pheochromocytoma patients (-21 +/- 7 mm Hg) than in normotensive subjects (-5 +/- 2 mm Hg) or essential hypertensive patients (-3 +/- 2 mm Hg) (P < .005 for both), whereas heart rate tended to increase most in the pheochromocytoma group. Postural reduction in systolic blood pressure was highly correlated with postural increase in heart rate (reciprocal change in RR interval) in the pheochromocytoma group (r = 0.716, P < .01) suggesting that baroreflex is well functioning in those patients. The Mayer wave power spectrum in recumbency was extremely depressed in pheochromocytoma patients (1.1 +/- 0.2 mm Hg2) compared with normotensives (4.5 +/- 0.8 mm Hg2) or essential hypertensives (5.6 +/- 0.6 mm Hg2) (P < .001 for both). This parameter increased significantly with standing in all groups but remained lower in patients with pheochromocytoma (5.1 +/- 1.0 mm Hg2) than in normotensives (7.1 +/- 0.9 mm Hg2, P = NS), whereas essential hypertensive patients demonstrated far greater value (19.2 +/- 3.8, P < .01 for both). The respiratory power spectrum of the RR interval in recumbency of pheochromocytoma patients (189 +/- 54 msec2) was less than in normotensive subjects (714 +/- 100 msec2, P < .001) but did not differ from that in patients with essential hypertension (214 +/- 41 msec2). The respiratory power spectrum of the RR interval upon standing was markedly suppressed in pheochromocytoma patients (36.9 +/- 16.7 msec2) compared with normotensive subjects (129.5 +/- 23.6 msec2) or essential hypertensive patients (126.6 +/- 28.6 msec2) (P < .001 for both). Postural decrement in the respiratory power spectrum of the RR interval correlated positively with postural increase in heart rate (r = 0.577, P < .05) in patients with pheochromocytoma. After successful surgery (n = 9), the Mayer wave power spectrum of the systolic blood pressure and the blood pressure response to orthostasis were normalized. These data suggest that altered sympathetic vascular regulation is central to the pathogenesis of orthostatic hypotension in pheochromocytoma, whereas cardiac vagal regulation acts to compensate.