Steatohepatitic hepatocellular carcinoma: imaging findings with clinicopathological correlation.

AIM: To evaluate the clinicopathological and computed tomography (CT) and magnetic resonance imaging (MRI) findings of steatohepatitic hepatocellular carcinoma (SH-HCC). MATERIALS AND METHODS: Clinicopathological and radiological features were evaluated in 20 patients with SH-HCC. The diagnosis of SH-HCC was made histologically if the tumour had four of the following five characteristics: steatosis (>5% tumour cells), ballooning, Mallory-Denk bodies, interstitial fibrosis, and inflammation. All patients underwent dynamic CT and MRI. CT and MRI images were reviewed for morphological features including tumour size, presence, and distribution of fat, and patterns and degree of contrast enhancement. RESULTS: Obesity, hypertension, and history of heavy alcohol intake were common clinical findings observed in 10 (50%), 13 (65%), and 11 (55%) of the 20 patients, respectively. Steatosis and steatohepatitis were pronounced in the background liver in 12 (60%) and 10 (50%) patients, respectively. SH-HCC was moderately differentiated in 18 patients (90%) and well differentiated in two (10%). Pathologically, steatohepatitic features were diffuse in 12 (60%) of the 20 tumours and focal in eight (40%). Tumour size and the percentage of intratumoural steatosis were not correlated (r=0.17, p=0.47). On CT, 16 (80%) patients showed arterial phase enhancement and delayed washout. On MRI, 16 (80%) of 20 tumours showed prominent fatty deposition (10 diffusely, six focally) with arterial phase enhancement. CONCLUSIONS: SH-HCC is likely to show prominent fatty deposits with arterial phase enhancement on CT and MRI. A hypervascular lesion with prominent fatty change should raise the diagnostic suspicion of SH-HCC.

Virtual monochromatic image at lower energy level for assessing pancreatic ductal adenocarcinoma in fast kV-switching dual-energy CT.

AIM: To evaluate the value of virtual monochromatic images (VMIs) at lower energy levels in fast-voltage-switching dual-energy computed tomography (DECT) for assessing pancreatic ductal adenocarcinoma (PDAC). MATERIALS AND METHODS: The institutional review board approved this prospective study. Written informed consent was obtained from all patients. Seventy-four consecutive patients with PDAC underwent dynamic contrast-enhanced DECT. Two radiologists reviewed eight energy levels (40, 45, 50, 55, 60, 65, 70, and 75 keV) of the pancreatic parenchymal phase VMIs. CT attenuation of the PDAC and pancreatic parenchyma, background noise, signal-to-noise ratio (SNR) of the pancreas, tumour-to-pancreas contrast-to-noise ratio (CNR), major and minor axes of PDAC, and qualitative tumour conspicuity were compared among the VMIs at eight energy levels. RESULTS: CT attenuation of PDAC and pancreatic parenchyma, background noise, SNR, and CNR peaked on VMIs at 40 keV with statistically significant difference (p<0.0001) and gradually decreased with increasing energy levels. The reproducibility in measuring tumour size was better on VMIs at 40 keV (28.8 and 29.2 mm of major axis in readers 1 and 2, respectively) and tended to be overestimated at higher energy levels (29.8 and 30.9 mm of major axis at 75 keV in readers 1 and 2, respectively). Qualitative tumour conspicuity was also significantly superior on VMIs at 40 keV than at all other energy levels (p<0.0001). CONCLUSION: VMIs at 40 keV demonstrated significantly increased SNR of the pancreas, CNR, and tumour conspicuity and high reproducibility in measuring tumour size for assessing PDAC.

Pancreatic MRI associated with pancreatic fibrosis and postoperative fistula: comparison between pancreatic cancer and non-pancreatic cancer tissue.

AIM: To evaluate the potential value of magnetic resonance imaging (MRI) for predicting postoperative pancreatic fistula (POPF) in patients with pancreatic cancer (PC) and non-pancreatic cancer (non-PC). MATERIAL AND METHODS: This retrospective study was approved by the institutional review board and written informed consent was waived. Forty patients underwent pancreatoduodenectomy due to PC (n=31) and non-PC (n=9). The pancreas-to-muscle signal intensity ratio (SIR) on three-dimensional (3D)- fast field echo (FFE) T1-, in- and opposed-phase T1-, and T2-weighted images, as well as the apparent diffusion coefficient (ADC) value of the pancreas were measured. The frequency of POPF and MRI measurements were compared between patients with PC and non-PC. The MRI measurements were also compared with the grade of pancreatic fibrosis on pathological findings, fat deposition, and interstitial oedema. RESULTS: The frequency of POPF was significantly higher in patients with non-PC than in those with PC (p=0.0067), with an odds ratio of 10.4. The SIR on 3D-FFE T1-weighted images was significantly higher in patients with non-PC (p=0.0001) and those with POPF (p=0.017) than in those with PC and those without POPF, respectively. Multiple regression analysis demonstrated that the SIR on 3D-FFE T1-weighted image was independently associated with the grade of pancreatic fibrosis (p<0.0001). CONCLUSION: The frequency of POPF was significantly higher in patients with non-PC than in those with PC was inversely related to the grade of pancreatic fibrosis. The SIR on 3D-FFE T1-weighted image might be a potential imaging biomarker for predicting POPF.

Right adrenal vein: comparison between adaptive statistical iterative reconstruction and model-based iterative reconstruction.

AIM: To compare right adrenal vein (RAV) visualisation and contrast enhancement degree on adrenal venous phase images reconstructed using adaptive statistical iterative reconstruction (ASiR) and model-based iterative reconstruction (MBIR) techniques. MATERIAL AND METHODS: This prospective study was approved by the institutional review board, and written informed consent was waived. Fifty-seven consecutive patients who underwent adrenal venous phase imaging were enrolled. The same raw data were reconstructed using ASiR 40% and MBIR. The expert and beginner independently reviewed computed tomography (CT) images. RAV visualisation rates, background noise, and CT attenuation of the RAV, right adrenal gland, inferior vena cava (IVC), hepatic vein, and bilateral renal veins were compared between the two reconstruction techniques. RESULTS: RAV visualisation rates were higher with MBIR than with ASiR (95% versus 88%, p=0.13 in expert and 93% versus 75%, p=0.002 in beginner, respectively). RAV visualisation confidence ratings with MBIR were significantly greater than with ASiR (p<0.0001, both in the beginner and the expert). The mean background noise was significantly lower with MBIR than with ASiR (p<0.0001). Mean CT attenuation values of the RAV, right adrenal gland, IVC, and hepatic vein were comparable between the two techniques (p=0.12-0.91). Mean CT attenuation values of the bilateral renal veins were significantly higher with MBIR than with ASiR (p=0.0013 and 0.02). CONCLUSION: Reconstruction of adrenal venous phase images using MBIR significantly reduces background noise, leading to an improvement in the RAV visualisation compared with ASiR.

P450 oxidoreductase deficiency with maternal virilization during pregnancy.

PURPOSE: The authors report on a rare case of maternal virilization during pregnancy caused by autosomal recessive P450 oxidore- ductase (POR) deficiency. MATERIALS AND METHODS: A 24-year-old primigravida developed a deepening voice and hirsutism in the second trimester. Prenatal ultrasonography failed to detect any fetal abnormality and fetal growth was normal. POR deficiency was suspected, but the mother declined fetal genetic testing. A female neonate was delivered by cesarean section at 41 weeks' gestation. RESULTS: The neonate had skeletal abnormalities. Mutational analysis of the POR gene demonstrated homozygosity for c.1370 G>A and p.R457H in the patient and heterozygosity in her parents. POR deficiency was confirmed in the neonate. CONCLUSION: POR deficiency should be suspected in cases of maternal virilization. Maternal urinary estriol, fetal magnetic resonance imaging, and parental genetic testing should be performed. Parental consent for fetal genetic testing should be sought to ensure prompt diagnosis and early treatment.

Development of a bioassay system for human growth hormone determination with close correlation to immunoassay.

Serum growth hormone (GH) level is measured largely through immunoassays in clinical practice. However, a few cases with bioinactive and immunoreactive GH have also been reported. We describe here a new bioassay system for GH determination using the BaF/GM cell line, which proliferates in a dose-dependent manner on hGH addition; cell proliferation was blocked by anti-hGH antibody. This bioassay had the lowest detection limit (∼0.02 ng/ml) reported thus far and the highest specificity for GH. The bioassay results were compared with those of an immunoradiometric assay across 163 patient samples in various endocrine states. A close correlation (the ratio of bioactivity/immunoreactivity was 1.04 ± 0.33, mean ± SD) was observed between bioactivity and immunoreactivity in these samples. The newly developed system is a specific, sensitive, easy, and fast bioassay system for GH determination; we consider it useful for evaluating GH bioactivity in various endocrine states.

Glycated albumin but not HbA1c reflects glycaemic control in patients with neonatal diabetes mellitus.

AIMS/HYPOTHESIS: It is difficult to use HbA(1c) as an indicator of glycaemic control in patients with neonatal diabetes mellitus (NDM) because of high levels of fetal haemoglobin (HbF) remaining in the blood. In this study, glycated albumin (GA), which is not affected by HbF, and HbA(1c) were compared to evaluate whether they reflect glycaemic control in patients with NDM. METHODS: This study included five patients with NDM. Age at diagnosis was 38 ± 20 days. Insulin therapy was started in all patients, and levels of GA, HbA(1c) and HbF were measured monthly for 6 months. One-month average preprandial plasma glucose (aPPG) was calculated using self-monitoring of blood glucose. RESULTS: Plasma glucose and GA were elevated (29.7 ± 13.1 mmol/l [n = 5] and 33.3 ± 6.9% [n = 3], respectively) but HbA(1c) was within normal limits (5.4 ± 2.6% [35.5 ± 4.9 mmol/mol]; n = 4) at diagnosis. With diabetes treatment, aPPG (r = -0.565, p = 0.002), GA (r = -0.552, p = 0.003) and HbF (r = -0.855, p < 0.0001) decreased with age, whereas HbA(1c) increased (r = 0.449, p = 0.004). GA was strongly positively correlated with aPPG (r = 0.784, p < 0.0001), while HbA(1c) showed no correlation with aPPG (r = 0.221, p = 0.257) and was significantly inversely correlated with HbF (r = -0.539, p = 0.004). CONCLUSIONS/INTERPRETATION: GA is a useful indicator of glycaemic control in patients with NDM, whereas HbA(1c) is influenced by age-related changes in HbF and does not accurately reflect glycaemic control.

Partial paternal uniparental disomy of chromosome 6 in monozygotic twins with transient neonatal diabetes mellitus and macroglossia.

Transient neonatal diabetes mellitus (TNDM) usually develops within the first few weeks of life and resolves at a median age of 3 months. In most of the cases, TNDM is caused by the over-expression of a paternally expressed imprinted PLAGL1 locus on chromosome 6q24. The most frequent manifestation other than TNDM is intrauterine growth retardation (IUGR), and in some cases macroglossia. We investigated monozygotic twins who had macroglossia without IUGR. Both of the twins developed insulin-dependent hyperglycemia within the first week of life, which subsequently resolved. DNA profiling with polymerase chain reaction amplification was performed for polymorphic microsatellite markers of chromosome 6. The six informative markers, located between 6p24 and 6q15, showed normal biparental inheritance. However, the six distal informative markers, located between 6q23.2 and the 6q telomeric region, showed the absence of a maternal allele and the presence of a single paternal allele. The monosomy of the 6q telomeric region was not confirmed by chromosome banding showing 46, XX. These findings provide further evidence that partial paternal uniparental disomy of chromosome 6 (pUPD6) causes TNDM. The phenotypes other than diabetes observed in patients with partial pUPD6 may differ from those observed in patients with complete pUPD6.

Muscarinic cationic current in gastrointestinal smooth muscles: signal transduction and role in contraction.

1 The muscarinic receptor plays a key role in the parasympathetic nervous control of various peripheral tissues including gastrointestinal tract. The neurotransmitter acetylcholine, via activating muscarinic receptors that exist in smooth muscle, produces its contraction. 2 There is the opening of cationic channels as an underlying mechanism. The opening of cationic channels results in influxes of Ca2+ via the channels into the cell and also via voltage-dependent Ca2+ channels which secondarily opened in response to the depolarization, providing an amount of Ca2+ for activation of the contractile proteins. 3 Electrophysiological and pharmacological studies have shown that the cationic channels as well as muscarinic receptors exist in many visceral smooth muscle cells. However, the activation mechanisms of the cationic channels are still unclear. 4 In this article, we summarize the current knowledge of the muscarinic receptor-operated cationic channels, focusing on the receptor subtype, G protein and other signalling molecules that are involved in activation of these channels and on the molecular characteristics of the channel. This will improve strategies aimed at developing new selective pharmacological agents and understanding the activation mechanism and functions of these channels in physiological systems.

Circadian rhythms of arginine vasopressin and vasoactive intestinal polypeptide do not depend on cytoarchitecture of dispersed cell culture of rat suprachiasmatic nucleus.

Dispersed cells of rat suprachiasmatic nucleus were cultured for more than a month with chemically defined medium. Arginine vasopressin and vasoactive intestinal polypeptide in the culture medium showed robust circadian rhythms starting 24 h after the cell dissociation. The two rhythms had similar periods, with a phase-lead of the vasoactive intestinal polypeptide peaks to the arginine vasopressin peak of about 1 h. The two rhythms remained two weeks later, with both peaks appearing at almost the same time, suggesting the synchronization of the two rhythms. Significant differences in cell architecture were detected depending on precoating matrices of culture dishes, which did not affect the circadian rhythms of arginine vasopressin and vasoactive intestinal polypeptide. Antimitotic treatment at the beginning of the culture not only reduced the number, but also changed the type of glial cells developed. The treatment did not interrupt the synchronized arginine vasopressin and vasoactive intestinal polypeptide rhythms until day 31. Early appearance of circadian rhythms indicates that neural networks in the suprachiasmatic nucleus are not necessary for the synchronous release of arginine vasopressin and vasoactive intestinal polypeptide. Glial proliferation is not essential for the generation, expression and synchronization of arginine vasopressin and vasoactive intestinal polypeptide rhythms in the dispersed suprachiasmatic nucleus cell culture.

Phase-dependent induction by light of rat Clock gene expression in the suprachiasmatic nucleus.

To clarify the role of Clock in the photic signal transduction of rat circadian clock, we cloned and sequenced rat Clock and examined the effect of a single light pulse on the Clock mRNA expression in the suprachiasmatic nucleus (SCN) by in situ hybridization. Rats were exposed to a 30 min light pulse ( approximately 300 lx) at one of six circadian phases in constant darkness (DD), and sacrificed 60 min after the light on. In the rats without light exposure, the mRNA level in the SCN was high at ZT (Zeitgeber time) 6 and low at ZT 18 and 22. Light exposure increased Clock mRNA level in the SCN in phase dependent manner. The mRNA level was significantly increased during the subjective night (ZT10-22). The light had no effect on the mRNA level during the subjective day (ZT2 and 6). The Clock mRNA was also detected in the piriform cortex (PC), and increased by light at ZT14. These results suggest that Clock transcription in the SCN is involved in the photic signal transduction of circadian clock in rats.

Long-term effects of niceritrol on serum lipoprotein(a) and lipids in patients with high levels of lipoprotein(a).

The long-term effects of niceritrol on lipoprotein(a) (Lp[a]), lipids, apolipoproteins, and fibrinogen and fibrinolytic factors were evaluated in 20 outpatients who had serum Lp(a) levels higher than 20 mg/dL. The mean ( +/- SE) levels of Lp(a) decreased from 33.6 +/- 2.3 mg/dL to 23.5 +/- 3.5 mg/dL after 12 months of niceritrol treatment (P < 0.01). Serum levels of triglycerides and apolipoprotein E decreased significantly and high-density lipoprotein cholesterol (HDL-C) increased significantly after 12 months (P < 0.05). There were no significant changes overall in fibrinogen and fibrinolytic factors, although fibrinogen concentrations showed a tendency to decrease with treatment. PAI-1 levels decreased significantly (P < 0.05) after 6 months of niceritrol treatment. A significant correlation of percent reduction between Lp(a) and apolipoprotein B levels (P < 0.01) was observed, suggesting that the Lp(a)-lowering effects of niceritrol may be due to niceritrol inhibition of apolipoprotein B synthesis, the major apolipoprotein of Lp(a). The ability of niceritrol to decrease Lp(a) levels and increase HDL-C levels, together with its tendency to lower fibrinogen levels, may help prevent coronary events in patients with high levels of Lp(a).

Results of duct-to-mucosa pancreaticojejunostomy for pancreaticoduodenectomy Billroth I type reconstruction in 100 consecutive patients.

BACKGROUND: This study retrospectively analyzed 100 consecutive patients who underwent pancreaticoduodenectomy (PD) and pylorus-preserving PD (PPPD) with a Billroth I type reconstruction and pancreaticojejunostomy by duct-to-mucosal anastomosis using a continuous running suture. STUDY DESIGN: Seventy patients underwent PD and 30 patients PPPD for pancreatic cancer in 33, bile duct cancer in 28, ampullary or duodenal tumor in 22, chronic pancreatitis in 8, and other gastrointestinal cancer in 9. Postoperative pancreatic anastomotic leakage was diagnosed from skin excoriation around the drain site, and was defined as a high concentration of amylase in drainage fluid or leakage demonstrated on x-ray. RESULTS: The mortality rate was 2% overall (2.8% in PD, 0% in PPPD). The morbidity rate was 23% overall (12.8% in PD, 46.7% in PPPD). Pancreatic anastomotic leakage was 4.0% overall (2.8% in PD, 6.7% in PPPD).. The incidence in the ampullary or duodenal tumors was 9.1% overall (0% in PD, 14.3% in PPPD). Biliary leakage occurred in four patients, 4.0% overall (4.3% in PD, 3.3% in PPPD), intraabdominal hemorrhage in 2% (2.8% in PD, 0% in PPPD), and lethal anastomotic leakage in one patient, overall rate 1% (1.4% in PD, 0% in PPPD). Delayed gastric emptying had the highest morbidity and was seen exclusively in PPPD (39.3%). CONCLUSIONS: A simple continuous running suture and parachuting for duct-to-mucosal pancreaticojejunostomy makes pancreaticoduodenectomy a safe procedure, even in a Billroth I type reconstruction.

Circadian rhythms and light responsiveness of mammalian clock gene, Clock and BMAL1, transcripts in the rat retina.

Circadian expression and light-responsiveness of the mammalian clock genes, Clock and BMAL1, in the rat retina were examined by in situ hydbribization under constant darkness. A small but significant daily variation was detected in the Clock transcript level, but not in BMAL1. Light increased the Clock and BMAL1 expressions significantly when examined 60 min after exposure. The light-induced gene expression was phase-dependent for Clock and peaked at ZT2, while rather constant throughout the day for BMAL1. These findings suggest that Clock and BMAL1 play different roles in the generation of circadian rhytm in the retina from those in the suprachiasmatic nucleus. Different roles are also suggested between the two genes in the photic signal transduction in the retina.

Circadian rhythm and light responsiveness of BMAL1 expression, a partner of mammalian clock gene Clock, in the suprachiasmatic nucleus of rats.

To clarify whether BMAL1 is involved in the photic signal transduction in the mammalian circadian clock, we examined the effects of a single light pulse on the level of BMAL1 mRNA in the suprachiasmatic nucleus (SCN) of rats by in situ hybridization. Rats were exposed to 30 min light of ca. 300 lux at six different phases in constant darkness and decapitated 60 min later. BMAL1 transcripts in the SCN of the control animals showed a robust circadian oscillation with the highest expression at ZT (Zeitgeber time) 18 and the lowest at ZT2. The light pulse slightly increased the level of BMAL1 transcripts in the SCN. However, the increment did not depend on the phase of light pulse. There was no significant change in the BMAL1 mRNA level up to 120 min after a light pulse at ZT14 and ZT22. These results indicate that BMAL1 transcription is not involved in the photic signal transduction responsible for non-parametric entrainment of the circadian clock in rats.

Daily variation and light responsiveness of mammalian clock gene, Clock and BMAL1, transcripts in the pineal body and different areas of brain in rats.

Expression patterns of mammalian clock genes, Clock and BMAL1, were examined by in situ hybridization in the pineal body, olfactory bulb, hippocampus and cerebellum in rats under constant darkness. In the pineal, the level of Clock transcript was significantly higher at ZT18 (subjective night) than at ZT6 (subjective day), while the level of BMAL1 transcript was significantly higher at ZT6 than at ZT18. A 30 min light pulse did not affect the transcript levels of Clock nor of BMAL1. The Clock expression in the cerebellum was significantly increased at ZT6 than at ZT18, while no difference was detected in the olfactory bulb and hippocampus at these two phases. The BMAL1 expressions in these areas were similar to the case in the pineal. These findings indicate that the mammalian clock gene, Clock and BMAL1, are expressed differently in the different areas of the brain and the pineal.

Efficacy of an echo contrast agent, SH/TA-508, in color doppler sonography of mass lesions in urology.

We performed a clinical phase III study with a galactosebased ecoo contrast agent, SH/TA-508, to evaluate its efficacy, safety, and usefulness for mass lesions in urology. SH/TA-508 was prepared as a suspension containing stabilized micro-air bubbles by adding water for injection just before use. SH/TA-508 was administered into the antecubital vein at an initial dose of 300 mg/ml × 5 ml followed by higher doses of 400 mg/ml × 4 ml, 300 mg/ ml × 10 ml or 400 mg/ml × 8 ml when a sufficient effect was not obtained. Efficacy was evaluated by color Doppler signal enhancement, the duration of blood flow signal enhancement, and improvement of diagnostic capacity. Fifty-nine patients with mass lesions in the kidney, prostate, testis, adrenal gland, and bladder were enrolled in the study. Up to the third dose the cumulative efficacy rates (≥2+) of color Doppler signal enhancement and duration of blood flow signal enhancement were 92% and 87%, respectively. Consequently, diagnostic capacity in 76% of the patients was remarkably improved. A light transient angialgia occurred in one patient but no other clinically significant changes were observed. It was confirmed that SH/TA-508 is a safe echo contrast agent that offers satisfactory color Doppler signal enhancement in the urologic organs mentioned above.

Small ileal neurofibroma causing intussusception in a non-neurofibromatosis patient.

Neurofibromas in the small intestine are usually accompanied by von Recklinghausen's disease (neurofibromatosis), and usually originate in the intramuscular plexus of Auerbach. We present here a solitary neurofibroma, which caused an ileocolic intussusception, originating in the submucosal plexus of Meissner in a non-neurofibromatosis patient. To our knowledge, there is no previous report of a neurofibroma originating in the plexus of Meissner. This condition was clearly confirmed by macroscopic and microscopic evaluation.

Endoscopic balloon dilation for benign esophageal anastomotic stricture: factors influencing its effectiveness.

BACKGROUND/AIMS: The aim of this study was to identify factors that might affect the results of treating benign anastomotic stricture of the esophagus with balloon dilation. METHODOLOGY: Balloon dilation was performed on 35 patients with benign esophageal anastomotic stricture of the upper (esophageal cancer: 18) or lower (gastric cancer: 15, esophageal varices: 2) esophagus. The procedure was considered effective when patients were able to maintain a solid diet more than 12 months after the last dilation. The follow-up period ranged from 15-130 months (mean: 51 months). RESULTS: A total of 245 dilations were performed, with an average of 6.6 dilations per patient. Treatment was effective in 29 patients (83%). Balloon dilation was successful when treating strictures shorter than 12 mm in length. The strictures were significantly shorter in patients treated effectively (5.6 vs. 30.8 mm). The diameter of the stricture did not affect the results. All the strictures in the lower esophagus and all those resulting from stapled anastomoses were treated successfully, while the effectiveness of treating strictures in the upper esophagus or those resulting from hand-sewn anastomoses was 67% and 57%, respectively. Strictures without prior leakage were treated effectively 92% of the time, while the success rate fell to 56% if there was a preceding leak. An average of 4.4 dilations were performed in effective cases, while the average was 17.5 dilations in ineffective cases. The number of repeat dilations was correlated with the length of the stricture. CONCLUSIONS: Balloon dilation can successfully treat strictures shorter than 12 mm long. The correlation equation may be used to predict the number of repeat dilations and treatment results, and is useful for deciding when to use an alternative method to balloon dilation.

Left ventricular performance at rest and during exercise in patients with dual-chamber pacemakers.

In 13 patients with an implanted dual-chamber atrioventricular (AV) demand pacemaker, left ventricular performance was elicited by pacing mode manipulation for study using gated cardiac pool scintigraphy at rest and during exercise. There was no significant difference between DDD and VVI at 70 and 90 beats/min with respect to cardiac output, peak ejection rate or peak filling rate. At 110 beats/min, the cardiac output was greater with DDD as compared to VVI. The peak filling rate was also significantly greater with DDD as compared to VVI (DDD: 3.6 vs VVI: 2.8 EDV/s, p less than 0.05). During exercise the cardiac output was greater with DDD as compared to VVI at the same rate. The peak filling rate during exercise was significantly greater with DDD as compared to VVI (DDD: 3.0 vs VVI: 2.5 EDV/s, p less than 0.01). We conclude that DDD is more beneficial than VVI in maintaining cardiac performance during exercise.