A case of aldosterone-producing adrenocortical adenoma associated with a probable post-operative adrenal crisis: histopathological analyses of the adrenal gland.

We describe a case of aldosterone-producing adrenocortical adenoma (APA) associated with a probable post-operative adrenal crisis possibly due to subtle autonomous cortisol secretion. The patient was a 46-year-old female who suffered from severe hypertension and hypokalemia. CT and MRI scans revealed a 2-cm diameter adrenal mass. The patient's plasma aldosterone level was increased, and her plasma renin activity was suppressed, both of which findings were consistent with APA. Cushingoid appearance was not observed. Morning and midnight serum cortisol and plasma adrenocorticotropic hormone (ACTH) levels were all within the normal range. Her serum cortisol level was suppressed to 1.9 microg/dl as measured by an overnight 1-mg dexamethasone suppression test, but was incompletely suppressed (2.7 microg/dl) by an overnight 8-mg dexamethasone suppression test. In addition, adrenocortical scintigraphy showed a strong uptake at the tumor region and a complete suppression of the contra-lateral adrenal uptake. After unilateral adrenalectomy, she had an episode of adrenal crisis, and a transient glucocorticoid replacement improved the symptoms. Histopathological studies demonstrated that the tumor was basically compatible with APA. The clear cells in the tumor were admixed with small numbers of compact cells that expressed 17alpha-hydroxylase, suggesting that the tumor was able to produce and secrete cortisol. In addition, the adjacent non-neoplastic adrenal cortex showed cortical atrophy, and dehydroepiandrosterone sulfotransferase immunoreactivity in the zonae fasciculata and reticularis was markedly diminished, suggesting that the hypothalamo-pituitary-adrenal (HPA) axis of the patient was suppressed due to neoplastic production and secretion of cortisol. Together, these findings suggested that autonomous secretion of cortisol from the tumor suppressed the HPA axis of the patient, thereby triggering the probable post-operative adrenal crisis. Post-operative adrenocortical insufficiency should be considered in clinical management of patients with relatively large APA, even when physical signs of autonomous cortisol overproduction are not apparent.     

Prevalence of non-alcoholic steatohepatitis (NASH) among biopsied cases of a urban hospital in Japan: significance of measurement of serum ferritin in the detection of NASH]

From April 1989 to December 2004, we performed liver biopsy on 475 patients and obtained biopsy proven 35 cases of non-alcoholic fatty liver. Among them, 18 cases were diagnosed as non-alcoholic steatohepatitis (NASH). During the last three years, we have tried to detect NASH using ultrasonography and elevated value of serum ferritin (> 300 ng/ml). All of the eligible 7 cases biopsied during the course were diagnosed as NASH. In these 7 cases, ALT levels improved after the body weight loss accompanied by the parallel decrease of serum ferritin levels. Measurement of serum ferritin is useful in the detection of NASH but the normal value of ferritin cannot rule out the possibility of NASH.     

New hepatic vein reconstruction in left liver graft.

The incidence of hepatic venous stenosis is higher in partial liver transplantation. New methods for hepatic venous reconstruction in left liver transplantation, which secure wide anastomosis, were devised and are reported here. In the graft, the right side of the middle hepatic vein or the left side of the left hepatic vein was cut longitudinally and a rectangular-shaped vein patch was attached for venoplasty. In the recipient, after the left and middle hepatic veins were joined, the right side of the middle hepatic vein was cut toward the closed right hepatic vein, making a horizontal cavotomy for anastomosis. Of 92 patients who underwent conventional hepatic vein reconstruction, 3 were complicated by hepatic venous stenosis (median follow-up 43 months). By contrast, there were no hepatic vein complications in the 20 patients who underwent the new technique (7 months). The current method appears to be technically feasible for outflow reconstruction in left liver graft transplantation.     

Clinical experience of hyperthermia in malignant tumors

Results in 44 cases of malignant tumors treated by localized radiofrequency hyperthermia are presented. All patients had either one or more failed attempts at conventional therapy or had such advanced disease at presentation that control with conventional modalities was considered unlikely. Hyperthermia were used together with radiation in 42 patients with chemotherapy in 1 patient, and alone in 1 patient. The overall response (CR plus PR) was 50% including a 18% complete response. Tumor response was somewhat better for superficial tumors. We retrospectively have analyzed the association between tumor response and histology, tumor size, temperature, radiation dose and total number of heat sessions. Clinical factors influencing the tumor response were initial tumor size and intratumor temperature. The incidence of overall response increased with a decrease in initial tumor size and an increase of intratumor temperature.     

Preparation and Characterization of a Murine Monoclonal Antibody (MDR3M) Reactive with mdr3 Gene Product

A murine monoclonal antibody (MDR3M) (isotype: IgM) reactive with mdr3 gene product was generated by immunizing mice with mdr3 -specific peptide (H₂N-¹²WRPTSAEGDFELGISSKQKRKKTKTVKMI⁴¹G-COOH) and hybridizing the primed mouse splenic B cells with X63-Ag8,6.5.3 mouse plasmacytoma cells. MDR3M did not cross-react with mdr1 gene product. This monoclonal antibody may be useful for analyzing the role of mdr3 gene product in cells and tissues.     

Effects of nitric oxide synthase inhibitors on gastric alkaline secretion in rats.

The effects of NG-nitro-L-arginine methyl ester (L-NAME), the nitric oxide (NO) synthase inhibitor, on gastric HCO3- secretion were examined in anesthetized rats. Intravenous administration of L-NAME (1, 2.5, 5 mg/kg) increased HCO3- secretion in a dose-related manner. This effect of L-NAME was mimicked by NG-mono-methyl-L-arginine (50 mg/kg, i.v.) and was antagonized significantly by concurrent administration of L-arginine but not D-arginine (200 mg/kg, i.v.). These results indicate that gastric HCO3- secretion is stimulated by inhibition of NO biosynthesis.     

Antitumor activity of orally administered streptococcal preparation, OK-432 on murine solid tumors and its absorption from the gut

OK-432 is an immunopotentiator which is normally administered by injection. In the present study, the antitumor activity of orally administered OK-432 on various solid tumors and the absorption of OK-432 from the gut were studied. Orally administered OK-432 inhibited the growth of Meth-A and BAMC-1 fibrosarcomas which had been subcutaneously transplanted in BALB/c mice. Autoradiograms of mice which had been administered 14C-labelled OK-432 orally demonstrated the absorption of OK-432 from the gut, and about 6% of orally administered OK-432 was absorbed 24 hrs after its administration. Moreover, an immunofluorescent study using an anti-OK-432 antibody revealed specific fluorescence in the mesenteric lymph node of mice which had been orally administered with OK-432. These results suggest that oral administration of OK-432 may be a beneficial immunotherapy.     

POTASSIUM ACCELERATES URINARY SODIUM EXCRETION DURING SALT LOADING WITHOUT STIMULATING ATRIAL NATRIURETIC POLYPEPTIDE SECRETION

1. Effects of potassium (K) supplementation (100 mEq/day) on urinary sodium (Na) excretion and on the secretion of atrial natriuretic polypeptide (ANP) during salt loading (350 mEq/day) were studied in 12 healthy salt-resistant normotensives under strictly controlled metabolic ward conditions. 2. Urinary volume and Na excretion on the first day of the high salt period (HSP) were significantly greater in the K-supplemented group (KG) than in the control group (CG). 3. There was a significant gain in bodyweight after salt loading in both groups, with a significantly greater gain in CG on the second day of HSP. Haematocrit decreased significantly during salt loading in both groups, the degree of which was significantly greater in CG. 4. Plasma norepinephrine decreased significantly during salt loading in both groups, the degree of which was significantly less in KG than in CG. A significant increase in plasma ANP was observed in CG on and after the second day of HSP, while a significant increase in plasma ANP was observed on the fifth day of HSP in KG. 5. These findings indicate that K supplementation accelerates diuresis and natriuresis, resulting in moderate suppression of volume expansion induced by salt loading and that this accelerated diuresis and natriuresis is not a result of the action of ANP.     

Assessment of SPECT ventilation-perfusion imaging in patients with lung cancer

Ventilation and perfusion SPECT images during tidal breathing were studied in 15 cases of lung cancer using ^81mKr gas and ^99mTc-microspheres. Furthermore, functional images of V/Q ratio and Q/V ratio were prepared, and their clinical significance is descussed with reference to general lung function. There was a decreas in %VC and %FEV _1.0in 7 of 15 cases, and an increase of AaDo₂ in the blood gas analysis in 12 of 15 cases. Both planar and SPECT images showed ventilation and perfusion abnormalities in all 15 cases. Of these, 12 patients showed matched ventilation and perfusion defects, 2 patients a dead-space effect and 1 patient a shunt effect. In comparing planar and SPECT images, depiction of ventilation and perfusion impairments were equally clear in 11 cases, but in 3, showing a lobar or segmental defect with a shunt effect, the SPECT images were superior. In a patient with markedly impaired function of the affected lung, the remaining function could not be depicted by SPECT. From the above, it seems that better information can be obtained for understanding the ventilation and perfusion states of lung cancer by adding the SPECT images to the planar image.