Femoral osteomyelitis due to Cladophialophora arxii in a patient with chronic granulomatous disease.

Fungal infections in patients with chronic granulomatous disease (CGD) are a poor prognostic factor. We describe the first case of CGD with femoral osteomyelitis due to Cladophialophora arxii, which is a member of the dematiaceous group. The causative fungus was identified on the basis of its morphological characteristics, growth temperature profile, and nucleotide sequence on the internal transcribed space region of the ribosomal gene. The patient was successfully treated with surgical debridement, subsequent administration of itraconazolem and interferon-gamma.

Antiproteinuric effect of the calcium channel blocker cilnidipine added to renin-angiotensin inhibition in hypertensive patients with chronic renal disease.

Cilnidipine, a dual L-/N-type calcium channel blocker, dilates both efferent and afferent arterioles and is renoprotective. Our multi-center, open-labeled, and randomized trial compared the antiproteinuric effect of cilnidipine with that of amlodipine in hypertensive patients with kidney disease. A group of 339 patients, already receiving renin-angiotensin system inhibitor treatment, were randomly assigned to cilnidipine or amlodipine. The primary endpoint was a decrease in the urinary protein to creatinine ratio. After 1-year of treatment, systolic and diastolic blood pressures were significantly reduced in both groups which did not differ between them. The urinary protein to creatinine ratio significantly decreased in the cilnidipine compared to the amlodipine group. Cilnidipine exerted a greater antiproteinuric effect than amlodipine even in the subgroup whose blood pressure fell below the target level. This study suggests that cilnidipine is superior to amlodipine in preventing the progression of proteinuria in hypertensive patients when coupled with a renin-angiotensin system inhibitor.

Effects of doxazosin on ambulatory blood pressure and sympathetic nervous activity in hypertensive Type 2 diabetic patients with overt nephropathy.

AIMS: Few studies have reported the effect of alpha(1)-adrenergic antagonists on 24-h blood pressure (BP) and sympathetic nervous activity in hypertensive patients with diabetic nephropathy. We assessed the effects of doxazosin on 24-h BP and spectral analysis of heart rate variability in hypertensive Type 2 diabetic patients with macroalbuminuria and compared the results with those in hypertensive Type 2 diabetic patients with normoalbuminuria and non-diabetic patients with essential hypertension. METHODS: Thirty-three patients in the macroalbuminuric group, 24 patients in the normoalbuminuric group, and 34 patients with essential hypertension underwent ambulatory BP monitoring before and after doxazosin treatment. Spectral analysis was performed to calculate the high-frequency (HF) components, a marker of parasympathetic nervous activity, and the low-frequency (LF) components, a marker of sympathetic nervous activity. RESULTS: Doxazosin decreased waking (from 158 +/- 17/88 +/- 10 to 148 +/- 15/80 +/- 7 mmHg, P = 0.001 for systolic and P < 0.001 for diastolic BP) and sleeping BP (146 +/- 20/79 +/- 10 to 137 +/- 17/72 +/- 9 mmHg, P < 0.001 and P < 0.001) in the macroalbuminuric group, but only decreased waking BP in the essential hypertension group (157 +/- 16/91 +/- 9 to 145 +/- 15/84 +/- 11 mmHg, P < 0.001 and P < 0.001) and normoalbuminuric group (159 +/- 15/89 +/- 9 to 150 +/- 16/82 +/- 10 mmHg, P = 0.014 and P < 0.001). Doxazosin decreased waking (from 1.48 +/- 0.11 to 1.42 +/- 0.12, P = 0.001) and sleeping (1.46 +/- 0.11 to 1.40 +/- 0.13, P = 0.001) LF components [unit: log(ms(2)/Hz)] only in the macroalbuminuric group without changing HF components. The normoalbuminuric and essential hypertension groups showed no differences (P = 0.637 and 0.492) in LF components during sleep. CONCLUSIONS: Doxazosin may be an antihypertensive agent that decreases both waking and sleeping BP through inhibiting sympathetic nervous activity in macroalbuminuric diabetes patients.

Different pathological findings in each of four parathyroid glands in a long-standing hemodialysis patient.

A 51-year-old male patient with chronic renal failure, who had required dialysis for 22 years, presented with a cervical mass. Laboratory data were consistent with secondary hyperparathyroidism due to chronic renal failure. Cervical exploration was performed with excision of four parathyroid glands and autotransplantation of the normal gland into the forearm. The cervical tumor of the right inferior gland demonstrated parathyroid carcinoma histologically. Adenoma of the right superior gland and hyperplasia of the left superior gland were also recognized. The left inferior gland was normal. A few cases of parathyroid carcinoma in patients on maintenance hemodialysis have been previously reported. However, this is the first report in which all four parathyroid glands revealed different pathological findings: carcinoma, adenoma, hyperplasia and normal gland. Chronic stimulation of the parathyroid glands to release parathyroid hormone might have caused the variety of findings in the four parathyroid glands.

Intensity modulation for breast treatment using static multi-leaf collimators.

PURPOSE: To achieve more uniform dose distributions in breast cancer treatment using multiple sets of multi-leaf collimator (MLC) defined fields. Dose uniformity for many breast cancer patients can be significantly improved by using two or more sets of portals and the "hot" regions of a traditional treatment can be significantly reduced. METHODS AND MATERIALS: Patients for breast cancer treatment are immobilized with alpha cradle in the traditional arm-up position and have a CT scan in the treatment position. The target volume is delineated on the 5-mm thick CT slices that are obtained from the lower neck to well below the breast target volume. Medial and lateral tangential fields at conventional gantry angles are designed with the aid of digitally reconstructed radiographs (DRRs). The MLC, without collimator rotation, is used to shape the field to spare as much lung as possible. The wedges and relative weights of the beams are optimized to provide the best dose uniformity. For the patients with large dose inhomogeneity, a second set of fields is designed. The weight of the original set of fields is reduced (usually to approximately 90%) so that the "original hot" regions receive the prescription dose; the second set of fields delivers a supplemental dose to the "cold" region, typically approximately 10% of the total dose. The second set of fields has the same beam parameters but "treat" only the part of breast tissue that is "cool." Presently, the design of the reduced field is an iterative process. The process can be extended to more than two sets of portals to obtain the desired dose uniformity. RESULTS: With 3D planning and multiple MLC fields, dose uniformity in the treatment of breast patients was improved from 7%-22% to approximately 7%-15%. The volume receiving these high doses decreased significantly and shifted from the lung to the target. By keeping the gantry angles and wedges the same for the multiple fields, treatments can be delivered quickly and reliably. The internal mammary nodes (IM) can also be treated without including significant amount of lung or heart in the field. CONCLUSION: Dose uniformity can be significantly improved by using this intensity modulation technique to treat certain breast patients. With these static MLC fields creating the intensity modulation, the dose uniformity to the breast can be significantly improved and the hot region in lung reduced. There is no increase in setup complexity. The small increase in treatment time is insignificant.

Intravascular ultrasound imaging of atherosclerotic renal arteries: comparison between in vitro and in vivo studies.

BACKGROUND: Intravascular ultrasound (IVUS) imaging, a new modality, may be feasible and useful for the assessment of atherosclerotic renal arteries. However, comparison between in vivo and in vitro studies to confirm pathological changes corresponding with IVUS findings obtained from renal arteries was not fully evaluated. METHODS: We evaluated ultrasound images of 18 post-mortem human renal arteries and cross-sectional IVUS images of main renal arteries in five patients with renal artery stenosis (RAS) or essential hypertension. RESULTS: In vitro studies have shown that renal-artery images had three layers when the arteries had fibrous intimal thickening and medial hypertrophy. Renal arteries, in which the fibrous intima was not well developed, showed circumferentially homogeneous bright echoes. In patients with atherosclerotic RAS and essential hypertension, IVUS images showed hyperechoic areas in the renal arterial walls, probably due to atherosclerosis. Typical three-layered ultrasound appearance was not easily seen during in vivo studies. CONCLUSION: Our findings suggest that hyperechoic images can be a diagnostic clue of atherosclerosis However, in vitro results do not always correspond exactly to in vivo findings, and caution is needed when findings from in vitro IVUS imaging studies are applied to in vivo studies.

Long-term therapy with an ACE inhibitor, temocapril, reduces microalbuminuria in essential hypertension.

The present study was conducted to prospectively evaluate whether a new ACE inhibitor, temocapril, could modify urinary microalbumin excretion rate (UAE) in a group of hypertensive outpatients who had no evidence of renal impairment. Sixty-three outpatients (32 men and 31 women; mean age, 59.9 +/- 1.5 yr) with essential hypertension entered the study, all having been treated for at least 6 mo with dihydropyridine calcium-channel blockers (CCBs: nitrendipine, nisoldipine, or amlodipine). Their blood pressures (BPs) had been controlled to adequate levels with the CCBs. None had overt proteinuria (determined by Albustix) or abnormal serum creatinine levels. After 3 mo of baseline observation under the previous treatment, the subjects were randomly divided into two groups. In group A (n = 31), the previously used CCBs were switched to temocapril, 2 to 4 mg once daily for 12 mo, and BP was controlled at a level equivalent to that during CCB treatment. In group B (n = 32), the subjects were maintained on their previous treatment for a further 12 mo. The effect of temocapril on BP appeared to be clinically similar to that of the previously used CCBs, but it significantly decreased UAE as compared with the previous therapy. In group A, UAE decreased significantly (p < 0.01) from the baseline value of 38.9 +/- 5.1 mg/g creatinine (Cr) to 22.2 +/- 4.2 and 25.3 +/- 5.6 mg/g Cr at the 6th and 12th months of temocapril therapy, respectively. In contrast, in group B UAE was unchanged (baseline 39.8 +/- 6.6 mg/g Cr; 6 mo, 44.6 +/- 6.8; 12 mo, 45.9 +/- 7.7). In group A, 17 of 31 patients (54.8%) had abnormal UAE levels (> or = 29.5 mg/g Cr) during previous therapy with CCBs, but 6 mo after switching to temocapril 25 of these patients (80.6%) had normal UAE (< 29.5 mg/g Cr). In group B, 15 of 32 patients (46.9%) had abnormal UAE levels during the observation period, and these abnormal UAE levels remained unchanged; 17 of the 32 patients (53.1%) had abnormal UAE levels after a further 6 mo of continued CCBs therapy. We conclude that long-term therapy with temocapril may provide renal protection by reducing UAE even in hypertensive patients with no evidence of renal impairment.

Regulation of cAMP production in initial and terminal inner medullary collecting ducts.

BACKGROUND: The inner medullary collecting duct (IMCD) is composed of at least two functionally and morphologically distinct segments, the initial (IMCDi) and the terminal (IMCDt) portions. However, most studies of receptor signaling have been performed on cells obtained from the entire inner medulla. The purpose of this study was to determine whether the patterns of receptor-activated cAMP accumulation were different between these segments. METHODS: We measured cAMP accumulation stimulated by vasopressin and isoproterenol, and the effect of epinephrine in freshly dissected IMCDi and IMCDt segments cultured and IMCDi and IMCDt cells in primary culture. RESULTS: The maximum response to vasopressin was twofold higher in fresh IMCDt verus IMCDi (P < 0.05), however, it increased in cultured IMCDi by 40% verus fresh cells with no change in the response in fresh verus cultured IMCDt. The maximum response to isoproterenol was small in fresh cells but increased by five- and sixfold, respectively, in cultured IMCDi and IMCDt cells. alpha 2-Adrenoceptor stimulation almost completely inhibited both vasopressin and isoproterenol-stimulated cAMP accumulations in fresh IMCDi and IMCDt cells, but only partially inhibited either accumulation by 34 to 49% in cultured cells. CONCLUSIONS: (1) IMCDi and IMCDt cells are both subject to vasopressin and alpha 2- and beta-adrenergic regulation of adenylyl cyclase activity; (2) the relative influence of beta-adrenergic, alpha 2-adrenergic and V2 receptors to affect cAMP accumulation is altered in primary culture versus freshly dissected IMCD segments, suggesting that caution must be exercised in the extrapolation of data from cultured IMCD cells to in vivo models.

Effective dose in diagnostic radiology as a function of x-ray beam filtration for a constant exit dose and constant film density.

Individual organ absorbed dose and total effective dose for nine common radiographic projections were investigated as a function of half-value-layer, HVL, and total equivalent filtration for the following cases: (1) with the patient exit dose held constant and (2) with the film density held constant. As expected, the absorbed dose to organs proximal to the x-ray beam entry point tracked with skin dose as a function of HVL, whereas organ dose distal to the x-ray beam entry point was almost independent of HVL. Dose to organs near mid-line showed an intermediate HVL dependence. For the nine radiographic projections, increasing the total filtration from 1.5 to 4.0 mm Al while holding the kVp fixed resulted in mean decreases in the effective dose of 17% for the case of a constant exit dose, and 25% for a constant film density with a "400 speed" rare-earth screen-film system. The decreases in the mean skin entrance doses were 38% and 45%, respectively. With the screen-film system, the average effective dose decreased at 16% per mm of added Al between 1.5 and 2.5 mm Al total filtration, and at 7% per mm between 2.5 and 4.0 mm. These results partially support the NCRP Report No. 102 recommendation that the minimum filtration be 2.5 mm Al for general diagnostic x-ray tubes. They also suggest, using the linear no-threshold radiation risk model, that further significant reductions in stochastic risk to the U.S. population can be achieved by raising the minimum beyond 2.5 mm. Experience over a 12 year period in our tertiary care teaching hospital indicates that adding 1-1.5 mm Al filtration beyond the 2.5 mm minimum does not pose a problem in terms of additional tube loading or reduction in image quality. However, these issues need to be more formally addressed.

Cough-challenge trial with a new angiotensin-converting enzyme inhibitor, imidapril.

This study was conducted to examine whether imidaprilat, an active diacid of the angiotensin-converting enzyme (ACE) inhibitor imidapril, preferentially inhibits angiotensin I degradation rather than bradykinin degradation, and whether imidapril is less active than other ACE inhibitors in inducing cough in patients with hypertension. The effect of imidaprilat on the inhibition of pressor response to angiotensin I and augmentation of depressor response to bradykinin was compared with that of enalaprilat and captopril in anesthetized rats. To determine the incidence of cough associated with imidapril, patients with a history of ACE inhibitor-induced dry cough were enrolled in a randomized, open-labeled, crossover trial with two 6-week periods to be treated with imidapril or amlodipine, a calcium-channel blocker. The recurrence of cough was assessed during both treatments. In the animal study, there were no significant differences in the ratio of inhibition of pressor response to angiotensin I and the augmentation of depressor response to bradykinin among the ACE inhibitors. In the cough-challenge trial, a total of 60 patients with hypertension were enrolled in the study. Cough and cough related symptoms recurred in 98.3% of the patients (59/ 60) during imidapril therapy. In contrast, only two patients reported cough during treatment with amlodipine. These results indicate that imidapril has no selectivity in inhibiting angiotensin I- and bradykinin-degradation in rats, and that clinically it is not different from other ACE inhibitors in inducing cough in patients with hypertension.

Paternal effects in Drosophila: implications for mechanisms of early development.

The study of paternal effects on development provides a means to identify sperm-supplied products required for fertilization and the initiation of embryogenesis. This review describes paternal effects on animal development and discusses their implications for the role of the sperm in egg activation, centrosome activity, and biparental inheritance in different animal species. Paternal effects observed in Caenorhabditis elegans and in mammals are briefly reviewed. Emphasis is placed on paternal effects in Drosophila melanogaster. Genetic and cytologic evidence for paternal imprinting on chromosome behavior and gene expression in Drosophila are summarized. These effects are compared to chromosome imprinting that leads to paternal chromosome loss in sciarid and coccid insects and mammalian gametic imprinting that results in differential expression of paternal and maternal loci. The phenotypes caused by several early-acting maternal effect mutations identify specific maternal factors that affect the behavior of paternal components during fertilization and the early embryonic mitotic divisions. In addition, maternal effect defects suggest that two types of regulatory mechanisms coordinate parental components and synchronize their progression through mitosis. Some activities are coordinated by independent responses of parental components to shared regulatory factors, while others require communication between paternal and maternal components. Analyses of the paternal effects mutations sneaky, K81, paternal loss, and Horka have identified paternal products that play a role in mediating the initial response of the sperm to the egg cytoplasm, participation of the male pronucleus in the first mitosis, and stable inheritance of the paternal chromosomes in the early embryo.

[Catecholamine and dopamine].

Almost all the genes of the enzymes which synthesize and metabolize the catecholamines (dopamine, norepinephrine, epinephrine) have been cloned and the gene targeting technology have been applied to introduce the gene knockout mouse such as thyrosine hydroxylase and dopamine beta hydroxylase. At least nine adrenergic receptors and five dopamine receptors have been cloned, which include alpha 1A-, alpha 1 B-, alpha 1 D-, alpha 2 A-, alpha 2B-, alpha 2C-, beta 1-, beta 2-, beta 3-adrenergic receptors and D1-, D2-, D3-, D4-, D5-dopamine receptors. Transgenic mouse as well as gene knockout mouse of these genes have been also produced. Furthermore, intracellular signal transduction systems of the catecholamines have been clarified using molecular techniques, including nine subtypes of adenylyl cyclase. Using these cloned genes and transgenic and gene knockout mouse, more detailed features of the catecholamine systems and those receptors and intracellular signal transduction systems will be clarified in near future.

Characterization of bunazosin-sensitive alpha1-adrenoceptors in human renal medulla.

We studied the characteristics of bunazosin-sensitive alpha1-adrenoceptors in human renal medullae by using renal-clearance studies and radioligand-binding assay. In 12 patients with hypertension, renal-clearance studies demonstrated that bunazosin significantly increased renal blood flow from 683 +/- 82 (SD) to 829 +/- 103 ml/min (p < 0.05) and decreased renal vascular resistance from 0.18 +/- 0.02 to 0.14 +/- 0.02 mm Hg/(ml/min) (p < 0.05), but that prazosin had little effect on renal function. In a radioligand-binding assay, specific, saturable, and stereoselective [3H]bunazosin binding, with a single class of binding sites (Kd = 2.7 +/- 1.4 nM; Bmax = 44 +/- 16 fmol/mg protein; n = 11) was detected in membrane preparations of human renal medullae. The rank order of potency of antagonists that inhibited [3H]bunazosin-binding was bunazosin (Ki in nM = 49) > prazosin (57) > yohimbine (3,900) > propranolol (29,000), and that of agonists, l-norepinephrine (7,400) > l-epinephrine (19,000) > d-norepinephrine (71,000). The competition curves fit a one-site model. These findings suggest that bunazosin-sensitive alpha1-adrenoceptors exist in human renal medullae and participate in the regulation of renal hemodynamics.

Effect of epinephrine on cAMP accumulation in cultured rat inner medullary collecting duct cells.

In a previous study we have reported the existence of alpha2- and beta-adrenoceptors in cultured rat inner medullary collecting duct (IMCD) cells. In this report, we examined the effect of epinephrine on intracellular adenosine 3',5'-cyclic monophosphate (cAMP) accumulation and evaluated whether alpha2-adrenoceptors interact with beta-receptors, vasopressin receptors, and prostaglandin (PG) E2 receptors by measuring cAMP generation. Epinephrine stimulated cAMP accumulation in a dose-dependent manner [half-maximal effective concentration (EC50) = 300 nM]. Rauwolscine (10 microM) enhanced epinephrine effects, shifting the dose-response curve for epinephrine to the left (EC50 = 120 nM); however, beta-antagonists inhibited epinephrine-induced cAMP accumulation. Epinephrine (10 microM) inhibited cAMP accumulation maximally induced by isoproterenol (10 microM); this effect was reversed by rauwolscine (10 microM). Epinephrine inhibited vasopressin (100 nM)-induced cAMP accumulation but failed to inhibit PGE2 (10 microM)-induced cAMP accumulation. We conclude that epinephrine acts as an alpha2- and beta-adrenoceptor agonist and that alpha2-adrenoceptors interact with beta-adrenoceptors and vasopressin receptors but not with PGE2 receptors on cAMP accumulation. This suggests that alpha2-adrenoceptors play a physiological role via interaction with different hormone receptors.

The beta 1- and beta 2-adrenoceptor subtypes in cultured rat inner medullary collecting duct cells.

We investigated beta-adrenoceptor subtype(s) expressed in cultured rat inner medullary collecting duct (IMCD) cells. In radioligand binding assay, [125I]iodocyanopindolol bound to IMCD cell membranes, representing a single class of binding sites (dissociation constant = 96.1 pM, maximum binding capacity = 18.2 fmol/mg protein, n = 8). In competition studies, ICI-89406 (beta 1-antagonist) and ICI-118551 (beta 2-antagonist) bound with high affinity, fitting a two-site model. Isoproterenol increased intracellular adenosine 3',5'-cyclic monophosphate (cAMP) accumulation (half-maximal effective concentration = 200 nM). Propranolol completely inhibited isoproterenol-induced cAMP accumulation [half-maximal inhibitory concentration (IC50) = 270 nM]. ICI-89406 and ICI-118551 inhibited cAMP accumulation by 50% (IC50 = 1.5 microM and 1.7 microM, respectively). The combined addition of ICI-89406 and ICI-118551 resulted in a curve indistinguishable from that of propranolol. The beta 1- and beta 2-adrenoceptor mRNAs have been demonstrated using reverse transcription-polymerase chain reaction. In initial and terminal IMCD cells, propranolol (3 microM) inhibited isoproterenol-stimulated cAMP accumulation by 80%, whereas ICI-89406 (3 microM) and ICI-118551 (3 microM) resulted in only partial inhibition (50%). We conclude that both beta 1- and beta 2-adrenoceptors are expressed in initial and terminal IMCD cells in primary culture.

[A new protein titrator tape for self-assessment by outpatients with proteinuria].

l- have invented a new dipstick (protein titrator tape) for measuring the volume of protein excreted in the 24-hour urine. The principle of the method is based on the protein error of indicators with the modification of a conventional dipstick test. The dipstick consists of two thick filter papers, containing differently adjusted pH indicators of tetrabromphenol blue, making it possible to detect a wide range of protein concentrations in the urine using a standard color chart that includes twenty color blocks. Two hundred and ninety outpatients had their urine samples assessed with this method as well as with the pyrogallol red test as a comparative study for quantitative measurement of protein concentrations. The new-type dipstick method exhibited good correlation with the results of the pyrogallol red test, especially in the range of protein concentrations from 50 mg/dl to 400 mg/dl, showing the linear equation of "y (Pyrogallol red) = 10.5 + 0.99 x (Dipstick) (r = 0.91, P < 0.01)". Although there was good correlation with the pyrogallol red test at higher concentrations from 400 mg/dl to 1,000 mg/dl, the dipstick method tended to exhibit lower concentrations than those indicated by the counterpart method. The rate of consistency between observers was quite high. This new-type dipstick method will offer a reliable method for patients or their family to assess their protein excretion in the urine every 24 hours at home using a portable urine sampling device.

Genetic characterization of ms (3) K81, a paternal effect gene of Drosophila melanogaster.

The vast majority of known male sterile mutants of Drosophila melanogaster fail to produce mature sperm or mate properly. The ms(3) K81(1) mutation is one of a rare class of male sterile mutations in which sterility is caused by developmental arrest after sperm entry into the egg. Previous studies showed that males homozygous for the K81(1) mutation produce progeny that arrest at either of two developmental stages. Most embryos arrest during early nuclear cycles, whereas the remainder are haploid embryos that arrest at a later stage. This description of the mutant phenotype was based on the analysis of a single allele isolated from a natural population. It was therefore unclear whether this unique paternal effect phenotype reflected the normal function of the gene. The genetic analysis and initial molecular characterization of five new K81 mutations are described here. Hemizygous conditions and heteroallelic combinations of the alleles were associated with male sterility caused by defects in embryogenesis. No other mutant phenotypes were observed. Thus, the K81 gene acted as a strict paternal effect gene. Moreover, the biphasic pattern of developmental arrest was common to all the alleles. These findings strongly suggested that the unusual embryonic phenotype caused by all five new alleles was due to loss of function of the K81+ gene. The K81 gene is therefore the first clear example of a strict paternal effect gene in Drosophila. Based on the embryonic lethal phenotypes, we suggest that the K81+ gene encodes a sperm-specific product that is essential for the male pronucleus to participate in the first few embryonic nuclear divisions.

Exaggerated blood pressure response to angiotensin II in patients with Cushing's syndrome due to adrenocortical adenoma.

We studied the roles played by the renin-angiotensin system in inducing hypertension in nine patients with Cushing's syndrome (CS) resulting from adrenocortical adenoma, and compared them with those in patients with primary aldosteronism (PA), renovascular hypertension (RVH) and essential hypertension (EH). In the CS group, each parameter, including serum potassium, plasma renin activity, plasma aldosterone, deoxycorticosterone and corticosterone concentrations, is within the normal range. However, plasma renin activity in the CS group was lower than that in the RVH group but higher than that in the PA group, and plasma aldosterone concentration was lower than that in each RVH or PA group. These findings indicated that the CS group had a different type of hypertension from that in either RVH or PA, in which the renin angiotensin system or mineralocorticoids play an important role in hypertension. Meanwhile, captopril (50 mg) administration either with or without indomethacin pretreatment decreased the mean blood pressure in the CS group, although captopril failed to change it in the PA group or in normal subjects. Furthermore, the pressor response to exogenous angiotensin II in the CS group was higher than that in the RVH or EH group, but was not different from that in the PA group. Thus, the hypertension in patients with CS due to adrenocortical adenoma appears to be mediated through a change in the renin-angiotensin system in the form of exaggerated pressor responses to angiotensin II.