Gallbladder carcinoma presenting as exfoliative dermatitis (erythroderma)

Although exfoliative dermatitis (erythroderma) secondary to malignancy is commonly associated with lymphomas or leukemias, coincident gastrointestinal (GI) malignancy and erythroderma is rare. The authors recently encountered a patient with gallbladder carcinoma presenting as erythroderma. A 77-yr-old Japanese man presented with a 3-mo history of erythematous eruptions with pruritus over almost the entire body. After confirming the diagnosis of erythroderma, asymptomatic gallbladder carcinoma was found. Further investigations detected no malignancies in other organs. An extended cholecystectomy was performed. Histologic examination of resected specimens revealed poorly differentiated adenocarcinoma with negative resection margins. The eruptions with pruritus resolved within 1 wk after the operation. This is the first report, to our knowledge, of coincident biliary malignancy and erythroderma. The experience of the current patient suggests that erythroderma secondary to GI malignancy may resolve spontaneously after curative resection of the tumor.     

Circadian dynamics of heart rate and physical activity in patients with heart failure

The present study was designed to develop a method to continuously measure Holter electrocardiogram (ECG) and physical activity in terms of metabolic costs to examine circadian dynamics of RR intervals and physical activity in patients with heart failure. A total of 7 healthy subjects and 3 heart failure patients performed cardiopulmonary exercise test using four-stage graded treadmill walking at 0% grade to examine whether the acceleration signals in the vertical direction could reflect actual body energy expenditure during physical activity. Then, using this new method, 24-hr monitorings of ECG and physical activity were performed in 24 inpatients with heart failure while they were allowed to walk around freely. Our results showed the integral of rectified acceleration signals was closely correlated with actual metabolic cost in all subjects. Instantaneous changes in heart rate were quite concordant with physical activity. As compared with the asymptomatic patients (n = 12), the symptomatic patients (n = 12) had lower energy expenditure during 8-hr daytime periods but higher mean heart rate. Furthermore, a more prominent ultradian rhythm of circadian changes in heart rate and physical activity was found in 50% of all subjects studied. The simultaneous analysis of Holter ECG and physical activity as the same time series revealed that in patients with heart failure, sympathovagal balance shifted toward sympathotonic conditions and their physical activity could become subject to intrinsic ultradian dynamics of body's homeostasis.     

Ventricular-load optimization in patients with heart failure.

The effects of unloading or inotropic agent in 22 patients with dilated cardiomyopathy were assessed in terms of optimal coupling between the ventricle and arterial system. In 13 patients (group A), lower body negative pressure (LBNP) was applied to reduce preload and nitroprusside was used to decrease afterload. In 9 patients (group B), dobutamine was used to enhance inotropic state. In all patients, the direct arterial pressure was simultaneously recorded with left ventricular echocardiogram as the pressure was elevated by phenylephrine. The left ventricular contractile properties were defined by the slope (Ees) of the end-systolic pressure-volume relation. The arterial system properties were expressed by the slope (Ea) of the end-systolic pressure-stroke volume relation. When the Ea/Ees ratio ranged from 0.5 to 1.0, both external work and mechanical efficiency are nearly maximized. In group A, baseline ventricular-load coupling was characterized by an increase in the Ea/Ees ratio (1.96 +/- 1.08) where the heart could maximize neither external work nor mechanical efficiency. Ea/Ees significantly fell to 1.45 +/- 0.77 with nitroprusside, while increasing to 2.37 +/- 1.17 during LBNP. In group B, Ea/Ees was decreased from 1.43 +/- to 0.82 +/- 0.47 with dobutamine. It is concluded that reduction in afterload rather than preload, or augmentation of contractility could restore optimal ventricular-load coupling in patients with severe cardiac dysfunction.     

Functioning adrenocortical oncocytoma: the first documented case producing interleukin-6 and review of the literature

Adrenocortical oncocytoma is an extremely rare and predominantly non-functioning tumor. We herein report the first case of an adrenocortical oncocytoma that produces interleukin (IL)-6. A 38-yr-old woman was referred for treatment of a 4-cm adrenal mass. Laboratory test results showed elevated inflammatory parameters. Intriguingly, IL-6 serum level was also high at 30 pg/ml (normal 0-4 pg/ml). The patient underwent laparoscopic right adrenalectomy. Microscopic examination showed that the tumor was an adrenocortical oncocytoma with a unique peripheral lymphoid cuff with germinal centers. Electron microscopy demonstrated that the cytoplasm of the neoplastic cells was packed with numerous abnormal mitochondria. Three observations lead us to consider that this tumor was the primary source of serum IL-6. First, the IL-6 level in blood collected from the right adrenal vein was highest (527 pg/ml) among intra-operative blood samples. Second, neoplastic cells stained positively for IL-6. Third, the serum IL-6 returned to normal levels immediately after surgery.     

Association analysis of the DISC1 gene with schizophrenia in the Japanese population and DISC1 immunoreactivity in the postmortem brain

The Disrupted-in-Schizophrenia 1 (DISC1) gene plays a role in the regulation of neural development. Previous evidence from genetic association and biological studies implicates the DISC1 gene as having a role in the pathophysiology of schizophrenia. In the present study, we explored the association between DISC1 missense mutation rs821616 (Ser704Cys) single nucleotide polymorphism (SNP) and four other SNPs (rs1772702, rs1754603, rs821621, rs821624) in the related haplotype block and schizophrenia in the Japanese population. We could not find a significant association of selected SNPs with schizophrenia after correction for multiple testing. We performed a meta-analysis of the Ser704Cys variant in schizophrenia using data from the present study and five previous Japanese population studies, and found no association with schizophrenia. We also examined DISC1 immunoreactivity in postmortem prefrontal cortex specimens of schizophrenia patients compared to control samples. The immunoreactivity revealed a significant decrease of DISC1 protein expression in the schizophrenia samples after ruling out potential confounding factors. However, the Ser704Cys variant did not show effects on DISC1 immunoreactivity. These results provide evidence that this functional genetic variation of DISC1 do not underlie the pathophysiology of schizophrenia in the Japanese population.