ABSTRACT
We report a patient with extrahepatically growing large hepatocellular carcinoma (HCC) associated with disseminated intraabdominal tumor and spontaneous tumor bleeding who was treated with four operations, transcatheter arterial embolization, systemic chemotherapy, and hyperthermia. It took 12 months for the multimodal treatment to normalize the alpha-fetoprotein (AFP) level, and remission continued for 6 months. We performed the fourth surgical treatment for a recurrent abdominal tumor involving the small intestine and mesentery, but the patient died 26 months after the first admission. Multimodal treatment, including repeat surgical treatments, for such advanced HCC should be encouraged, to prolong life and to maintain quality of life.
Subject(s)
Carcinoma, Hepatocellular/secondary , Carcinoma, Hepatocellular/therapy , Hepatectomy/methods , Liver Neoplasms/pathology , Liver Neoplasms/surgery , Peritoneal Neoplasms/secondary , Peritoneal Neoplasms/therapy , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Carcinoma, Hepatocellular/diagnosis , Combined Modality Therapy , Embolization, Therapeutic/methods , Follow-Up Studies , Humans , Hyperthermia, Induced/methods , Liver Function Tests , Liver Neoplasms/diagnosis , Male , Middle Aged , Peritoneal Neoplasms/diagnosis , Reoperation , Severity of Illness Index , Treatment OutcomeABSTRACT
Aldosterone selectivity in mineralocorticoid target tissues is mainly due to 11beta-hydroxysteroid dehydrogenase (11betaHSD), which converts cortisol to its inactive metabolite cortisone in humans. The defect of dehydrogenase activity would thus allow type 1 mineralocorticoid receptor (MR) to be occupied mostly by cortisol. It has been postulated that 11betaHSD type 2 (11betaHSD2) plays a significant role in conferring ligand specificity on the MR. We have demonstrated the diminished dehydrogenase activity in resistance vessels of genetically hypertensive rats. However, the mechanism that could link impaired vascular 11betaHSD activity and elevated blood pressure has been unclear. In this study, we showed the enzyme activity in human coronary artery smooth muscle cells. Glucocorticoids and mineralocorticoids increase vascular tone by up-regulating the receptors of pressor hormones such as angiotensin II (Ang II). Next, we found that physiological concentrations of a cortisol-induced increase in Ang II binding were significantly enhanced by the inhibition of dehydrogenase activity with an antisense DNA complementary to 11betaHSD2 mRNA, and the enhancement was partially but significantly abolished by a selective aldosterone receptor antagonist. This may indicate that impaired dehydrogenase activity in vascular wall results in increased vascular tone by the contribution of cortisol, which acts as a mineralocorticoid. In congenital 11betaHSD deficiency and after the administration of 11betaHSD inhibitors, suppression of dehydrogenase activity in the kidney has been believed to cause renal mineralocorticoid excess, resulting in sodium retention and hypertension. These results show that vascular 11betaHSD activity could influence blood pressure without invoking renal sodium retention.
Subject(s)
Coronary Vessels/enzymology , Hydroxysteroid Dehydrogenases/metabolism , 11-beta-Hydroxysteroid Dehydrogenases , Angiotensin II/metabolism , Cells, Cultured , Coronary Vessels/cytology , Coronary Vessels/metabolism , Humans , Hydrocortisone/pharmacology , Hydroxysteroid Dehydrogenases/antagonists & inhibitors , Hydroxysteroid Dehydrogenases/genetics , Muscle, Smooth, Vascular/cytology , Muscle, Smooth, Vascular/enzymology , Muscle, Smooth, Vascular/metabolism , Oligonucleotides, Antisense/pharmacologyABSTRACT
Effects of liquid paraffin on antibody responses and local adverse reactions after intramuscular injection of oil adjuvanted vaccines containing Newcastle disease (ND) and infectious bronchitis (IB) virus were investigated in chickens. Each vaccine was prepared with a liquid paraffin such as Carnation, Crystol 52 and Lytol. These vaccines induced sustained antibody responses against ND and IB. Among local adverse reactions, Lytol induced granulomatous reactions and abscesses, but Carnation and Crystol 52 did not. The residual weight of liquid paraffin at the injection site decreased in the order Carnation, Crystol 52, Lytol. Crystol 52 was composed of relatively few short-chain hydrocarbons (i.e.,
Subject(s)
Antibodies, Viral/biosynthesis , Chickens , Infectious bronchitis virus/immunology , Mineral Oil/administration & dosage , Newcastle disease virus/immunology , Viral Vaccines/immunology , Adjuvants, Immunologic/administration & dosage , Adjuvants, Immunologic/pharmacology , Animals , Antibodies, Viral/blood , Coronavirus Infections/immunology , Coronavirus Infections/prevention & control , Coronavirus Infections/veterinary , Emulsions , Gas Chromatography-Mass Spectrometry/veterinary , Hemagglutination Inhibition Tests/veterinary , Injections, Intramuscular/veterinary , Mineral Oil/chemistry , Neutralization Tests/veterinary , Newcastle Disease/immunology , Newcastle Disease/prevention & control , Specific Pathogen-Free Organisms , Vaccination/standards , Vaccination/veterinary , Viral Vaccines/administration & dosage , Viral Vaccines/adverse effectsABSTRACT
Dehydroevodiamine hydrochloride (0.1-0.3 mg/kg iv), which was isolated from the leaves of Evodia rutaecarpa, increased the cerebral blood flow recorded from the surface of the supra-sylvian gyrus in anesthetized cats. This action reached a maximum 1-4 min after injection and continued for 10 min. However, the compound had negligible effects on other cardiorespiratory functions at the doses examined. These results suggest that the compound selectively increases cerebral blood flow.
Subject(s)
Alkaloids/pharmacology , Cerebrovascular Circulation/drug effects , Drugs, Chinese Herbal/pharmacology , Alkaloids/isolation & purification , Anesthesia , Animals , Cats , Drugs, Chinese Herbal/chemistry , Female , Hemodynamics/drug effects , Male , Respiratory Function TestsABSTRACT
Endogenous digital-like substance (DLS) is increased in patients with essential hypertension and is hypothesized to play a role in the pathogenesis of high blood pressure. Whether an increase in DLS in diabetic patients with hypertension is associated with a family history of hypertension or diabetic nephropathy was investigated. Plasma DLS was measured as Na(+)-K(+)-ATPase inhibitory activity (ATPI) in 100 Type 2 diabetic patients. Ouabain was used as a standard of Na-K-ATPase inhibition. Diabetic patients with hypertension demonstrated a greater ATPI level than normotensive diabetic patients (p less than 0.05). In patients with hypertension groups, the positive family history group had a higher ATPI level than the negative family history group (p less than 0.01). Microalbuminuria was not correlated with the ATPI level in diabetic patients. These results suggest that ATPI might play a role in the pathogenesis of hereditary hypertension associated with diabetes mellitus, but not have etiologic significance in diabetic nephropathy.
Subject(s)
Diabetes Mellitus, Type 2/blood , Digitalis/metabolism , Hypertension/blood , Plants, Medicinal , Plants, Toxic , Aged , Albuminuria/complications , Blood Pressure/physiology , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/physiopathology , Diabetic Neuropathies/etiology , Female , Humans , Hypertension/etiology , Hypertension/genetics , Male , Middle Aged , Ouabain , Sodium-Potassium-Exchanging ATPase/antagonists & inhibitorsABSTRACT
The acute effects of the calcium entry blocker, nifedipine, on cerebral circulation were studied in 22 patients (56 +/- 5 years) with essential hypertension (EHT, WHO I-II) and 12 age-matched normal subjects. Cerebral effects were reevaluated in sixteen EHT patients after 8 weeks of treatment. The cerebrovascular resistance (Rp), cerebral capacitance (Cp), carotid velocity, and flow volume were measured by a newly developed ultrasonic volume flow meter coupled with a built-in computer which calculates Rp and Cp based on a simulated model. In EHT, acute administration of nifedipine (10 mg orally) decreased Rp from 13.5 +/- 1.8 to 8.0 +/- 0.3 (p less than 0.01) and increased Cp from 22.8 +/- 3.3 to 54.9 +/- 5.2 mFc (p less than 0.01). The carotid blood flow and velocity increased by 25.7% and 22.9%, respectively (p less than 0.05) in the face of lowered arterial pressure. In normal subjects, nifedipine also decreased Rp and increased Cp but to a lesser degree compared with EHT. The acute changes in cerebrovascular circulation in EHT were maintained at 8 weeks of treatment. These results suggest that nifedipine reduces Rp, possibly as the consequence of systemic hypotension and direct vasodilation of the cerebral arteries. This may be beneficial for hypertensive patients.
Subject(s)
Cerebrovascular Circulation/drug effects , Hydrochlorothiazide/therapeutic use , Nifedipine/therapeutic use , Adult , Aged , Blood Flow Velocity/drug effects , Blood Pressure/drug effects , Delayed-Action Preparations , Female , Humans , Long-Term Care , Male , Middle Aged , Vascular Resistance/drug effectsABSTRACT
A 59-year-old woman was admitted to our clinic with the complaint of left flank pain. Excretory urogram showed left hydronephrosis. Computed tomographic (CT) scan and renal angiography showed a left renal capsular tumor. Histological specimen obtained by a sure cut needle suggested malignant lymphoma. She was treated with a combined treatment of 8 MHz radiofrequency hyperthermia in a total of 10 sessions and 5,440 rads irradiation for 5 weeks. After the treatment, CT scan showed 92% tumor regression. After that, a recurrent tumor in left shoulder muscle became manifest. She received combination chemotherapy with 3 courses of ABEP regimen (aclacinomycin, cytosine arabinoside, etoposide, prednisolone) and 7 courses of ACOPE regimen (adriamycin, cyclophosphamide, vincristine, prednisolone, etoposide) and complete remission was obtained.
Subject(s)
Hyperthermia, Induced , Kidney Neoplasms/therapy , Lymphoma/therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Combined Modality Therapy , Female , Humans , Kidney Neoplasms/diagnostic imaging , Kidney Neoplasms/pathology , Lymphoma/diagnostic imaging , Lymphoma/pathology , Middle Aged , Radiography , Remission InductionSubject(s)
Asthma/therapy , Behavior Therapy , Breathing Exercises , Asthma/nursing , Humans , Male , Middle AgedABSTRACT
In order to investigate the possible role of mineralocorticoid in the regulation of digoxin-like substance (DLS), 9 alpha-fluorocortisol (9-F) was administered to 6 healthy men and urinary excretion of DLS was measured. The administration of 0.6 mg of 9-F caused slight increases in body weight and blood pressure and significant decreases in urinary Na excretion, plasma renin activity and plasma aldosterone, which indicate the expansion of extracellular fluid (ECF) volume by 9-F administration. Urinary excretion of DLS decreased significantly from the baseline level of 43.3 +/- 2.6 (SEM) to 29.8 +/- 5.1 (SEM) ng/day; digoxin equiv. after 9-F. These results suggest that a large dose of mineralocorticoid may suppress DLS despite an increase in the ECF volume.
Subject(s)
Blood Proteins/urine , Digoxin , Fludrocortisone/analogs & derivatives , Saponins , Water-Electrolyte Balance , Blood Proteins/immunology , Cardenolides , Cross Reactions , Extracellular Space/physiology , Fludrocortisone/pharmacology , Humans , Male , Steroids/immunologyABSTRACT
We describe the natural recovery from the aggravated hypertension, hypokalemia and suppression of the renin-aldosterone axis after the glycyrrhizin discontinuation in two mild hypertensive women aged 71 and 68 years, who had been administered 273 to 546 mg glycyrrhizin daily for 1.5 and 6 months, respectively, for the treatment of liver disease. About one month after the glycyrrhizin discontinuation, acceleration of hypertension, hypokalemia and suppression of the renin-aldosterone system still continued in both patients. At this stage, sodium restriction resulted in the normalization of blood pressure with weight loss and the subsequent sodium repletion produced a rapid increase in blood pressure to hypertensive levels observed before sodium restriction, with weight gain. Plasma renin activity and plasma aldosterone were low and did not respond to sodium restriction. Inappropriately excessive amounts of potassium were also excreted in the presence of hypokalemia. About one and a half months later, the improvements of aggravated hypertension, hypokalemia and suppressed renin-aldosterone system gradually occurred in both patients. Sodium restriction performed about three months later in case 2 no longer produced the changes in blood pressure and body weight. Plasma renin activity and plasma aldosterone responded subnormally to sodium restriction. These results demonstrate that both patients had a prolongation of the syndrome resembling primary aldosteronism except the low plasma aldosterone level about one month after the glycyrrhizin discontinuation. The possible mechanisms by which this prolongation was caused are discussed.
Subject(s)
Glycyrrhetinic Acid/analogs & derivatives , Hyperaldosteronism/chemically induced , Aged , Aldosterone/blood , Blood Pressure , Diet, Sodium-Restricted , Female , Glycyrrhetinic Acid/adverse effects , Glycyrrhiza , Humans , Hyperaldosteronism/blood , Hyperaldosteronism/physiopathology , Hypertension/chemically induced , Hypokalemia/chemically induced , Liver Diseases/drug therapy , Plants, Medicinal , Renin/blood , Time FactorsABSTRACT
The response of plasma aldosterone (PA) to ACTH administration (250 micrograms alpha 1-24 ACTH i.m.) before and during treatment with spironolactone (Sp, 75--100 mg/day) for at least 8 months was studied in 11 patients with essential hypertension. These responses were compared with those before and during prolonged treatment with hydrochlorothiazide (Th, 50--75 mg/day), with or without potassium supplement, in 14 hypertensives. PA and plasma cortisol (PC) were determined by radioimmunoassay in which Sp showed minimal cross-reactivity. Both Sp and Th treatments caused similar increases in plasma renin activity accompanied by nearly identical decreases in blood pressure and body weight. PA was also increased by both treatments, but to a significantly greater extent in the Sp-treated group. Serum potassium concentration was increased only by Sp treatment. The response of PA, but not of PC, to acute ACTH stimulation was blunted in the Sp-treated group. That is, the maximal increment of PA above the baseline level was significantly lower during Sp treatment than either before Sp treatment of during Th treatment. These results demonstrate that long-term treatment with Sp can inhibit aldosterone production by acute ACTH stimulation in patients with essential hypertension.