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Martin Reincke

Publications and source records attributed to Martin Reincke.

At least 19 recordsLinked to original sources
PubMed2007

[Diagnosis of primary hyperaldosteronism].

Primary hyperaldosteronism is the most common secondary form of hypertension. Diagnosis of this entity is recommended in hypokalemic hypertension, in therapy-resistant hypertension (at least three 3 drugs and RR > 140/90 mmHg), and in adrenal incidentalomas (= incidentally discovered adrenal tumors). For screening, the ratio between plasma aldosterone (PAC) and plasma renin concentration (PRC) should be measured. In the assessment of PAC/PRC ratio, the discontinuation of some antihypertensive medication and assay-specific cutoff values must be noticed. After a positive screening test, saline infusion test should be done as confirmatory test. In contraindications/impracticability of this test, 24-h urine collection for aldosterone-18-glucuronide under high-sodium diet can be used as alternative confirmatory test. After confirmation of primary hyperaldosteronism, differential diagnosis between aldosterone-producing adenoma and idiopathic hyperaldosteronism has to be done. For this approach, adrenal CT or MRT, posture test and adrenal vein catheterization as gold standard test are available. Whereas therapy of aldosterone-producing adenoma is surgery, idiopathic hyperaldosteronism is to be treated medically by spironolactone.

Adenoma↗
PubMed2006

Automated chemiluminescence-immunoassay for aldosterone during dynamic testing: comparison to radioimmunoassays with and without extraction steps.

BACKGROUND: Measurements of aldosterone have become more common since the recognition that primary aldosteronism is a more frequent cause of hypertension than previously believed. Our aim was to compare concentrations reported by 4 assays for samples obtained after saline infusion during dynamic testing. METHODS: We tested 104 participants (27 with primary aldosteronism, 30 with essential hypertension, and 47 healthy controls) with the intravenous saline infusion test (2.0 L isotonic saline over 4 h), with repetitive sampling. In all blood samples, aldosterone concentration was measured by an in-house RIA after extraction and chromatography, by 2 commercially available RIAs without extraction (Aldosterone Maia, Adaltis; Active Aldosterone, Diagnostics Systems Laboratories) and by an automated CLIA (Advantage, Nichols Institute Diagnostics). RESULTS: Correlation coefficients for results of pairs of assays ranged from 0.74 to 0.98. Agreement between commercial assays and in-house RIA was best at the low to intermediate concentrations after saline infusion. Mean (SD) Adaltis and DSL RIA results were 2- to 3-times higher [healthy participants: 78 (25) ng/L and 56 (18) ng/L, respectively] than those obtained by Nichols CLIA [17 (8) ng/L] and in-house RIA [23 (18) ng/L]. Aldosterone concentrations measured by the Nichols CLIA were below the limit of detection (limit of the blank) in 27 of 47 healthy participants. CONCLUSIONS: Aldosterone concentrations reported by the Adaltis and DSL nonextraction RIAs were consistently higher than those produced by the Nichols CLIA and the in-house RIA. The convenient Nichols CLIA showed better agreement with the in-house RIA, but the concentrations in healthy participants were frequently undetectable by this method. Uncritical application of cutoff values from the literature must be avoided.

Adult↗
PubMed2006

High-dose 17beta-estradiol treatment prevents development of heart failure post-myocardial infarction in the rat.

OBJECTIVES: Prognosis of heart failure remains poor despite therapeutic advances, such as angiotensin converting enzyme inhibition or beta-receptor blockade. Thus, more effective forms of treatment are urgently needed. Since estrogens have been shown to modulate migration and proliferation of cardiac fibroblasts and to modulate the expression of estrogen receptors of cardiomyocytes we examined whether high-dose estrogen treatment can affect post-myocardial infarction left ventricular remodeling. METHODS: Female rats were treated with 17beta-estradiol (7.5 mg/90 d) or placebo for ten weeks, starting two weeks prior to experimental myocardial infarction. Eight weeks after infarction, in vivo echocardiographic and hemodynamic measurements as well as isolated heart perfusion were performed. RESULTS: In vivo, chronic estrogen treatment almost completely prevented the development of all signs of heart failure that occur in untreated infarcted hearts, such as increased left ventricular diameters (dilatation), reduced fractional shortening (systolic dysfunction) or increased left ventricular end-diastolic pressure (diastolic dysfunction). In vitro, the right- (indicating structural dilatation) and downward (indicating left ventricular dysfunction) shift of left ventricular pressure-volume curves occurring in untreated infarcted hearts was completely prevented by estrogen. CONCLUSIONS: High dose estradiol treatment prevented development of post-MI remodeling, as assessed by in vivo and in vitro parameters of LV dysfunction. Estrogen may hold the potential of becoming a new form of heart failure treatment.However, the mechanisms responsible for this striking and unexpected beneficial action of estrogen in heart failure remain to be elucidated.

Animals↗
PubMed2006

Expression and spatio-temporal distribution of differentiation and proliferation markers during mouse adrenal development.

Development of the adrenal cortex is dependent upon the specific regulation of cellular proliferation and differentiation. Although both intra-adrenal transcription factors and extra-adrenal peptide hormones have been demonstrated as indispensable for this regulatory process, the resulting distribution of proliferating and steroidogenic cell populations in the developing adrenal cortex has not been defined. Thus, we assessed expression and colocalization of a differentiation marker (3-beta-hydroxysteroid dehydrogenase, 3beta-HSD) and a proliferation marker (5-bromo-2'-deoxyuridine (BrdU) incorporation) at the various time points (embryonic day (E) 9.5 until 2 weeks post partum) during mouse adrenal development. In addition, adrenocorticotropin-hormone (ACTH) receptor (melanocortin-2-receptor (MC2-R)) expression was examined by in situ hybridization (ISH) and co-localized with 3beta-HSD. As demonstrated by immunohistochemistry (IHC) the number of BrdU positive cells within the adrenal cortex decreased during development, whereas the number of 3beta-HSD positive cells increased. While BrdU incorporation was evident in a scattered pattern throughout the adrenal gland up to day E13.5, at later time points BrdU positive cells assembled in a discrete subcapsular compartment possibly representing the stem cell layer of the adult adrenal cortex. Interestingly, only a small percentage of proliferating cells expressed 3beta-HSD, while the majority of 3beta-HSD positive cells co-stained for MC2-R expression by means of ISH. As demonstrated by semiquantitative RT-PCR, MC2-R mRNA levels increased from E11.5 until birth, while the highest adrenal secretory protease (AsP) expression was detected at E13.5 with a decrease thereafter. Taken together, these findings are in accordance with the concept of distinct cell populations present during adrenocortical development with a highly proliferative phenotype or differentiated steroidogenic properties.

3-Hydroxysteroid Dehydrogenases↗
PubMed2006

Screening for primary aldosteronism.

Normokalaemic manifestation of primary aldosteronism is a frequent cause of secondary hypertension. It occurs in approximately 5-12% of all patients with hypertension, primarily patients with severe and uncontrolled blood pressure. Main causes are bilateral adrenal hyperplasia (2/3 of cases) and aldosterone-producing adenoma (1/3 of cases). Screening is performed by measurement of the aldosterone/renin ratio, which is raised in affected patients. Suspicion of primary aldosteronism due to a pathological ratio requires confirmatory testing e.g. by saline infusion test or fludrocortisone suppression test. If the diagnosis is confirmed, the underlying cause of aldosterone excess needs to be identified because therapy differs. First, adrenal imaging (CT/MRI) is performed, which is followed by postural testing in cases with a unilateral lesion. Concordant results confirm the diagnosis of an aldosterone-producing adenoma and allow treatment to proceed to adrenalectomy. In cases of equivocal results or normal/bilaterally enlarged adrenal glands on imaging, adrenal venous sampling must be performed for subtype differentiation.

Aldosterone↗
PubMed2006

Intraoperative haemodynamic stability in patients with phaeochromocytoma--minimally invasive vs conventional open surgery.

OBJECTIVE: There is conflicting evidence, whether or not minimally invasive adrenalectomy (MA) is associated with an increased perioperative cardiovascular instability in phaeochromocytomas compared to conventional open adrenalectomy (CA). DESIGN AND PATIENTS: In a retrospective analysis of 49 patients with phaeochromocytoma we compared 27 cases of MA to 22 cases of CA by assessing intraoperative haemodynamic parameters and perioperative complications. Patients undergoing MA for adrenocortical adenomas (aldosteronomas n = 15, inactive adenomas n = 13) served as controls. Additionally, we investigated the effect of phenoxybenzamine (POB) pretreatment on intraoperative cardiovascular stability in 42 patients (ranked by maximum daily POB-dose) by comparing the highest (n = 10) with the lowest (n = 10) POB dose quartile (0.32 +/- 0.2 and 2.17 +/- 0.6 mg/kg/day, P < 0.001). RESULTS: In phaeochromocytomas we found no significant difference in intraoperative haemodynamic parameters or complications when comparing MA with CA. In comparison to adrenocortical adenomas, MA in phaeochromocytomas was associated with a significantly higher maximum systolic BP (188 +/- 29 vs 154 +/- 22 mmHg, P < 0.001), more frequent hypertensive episodes (1[0-4]vs 0[0-1], P < 0.001), more episodes of systolic BP > 200 mmHg (0[0-4]vs 0[0-1], P = 0.03) and a higher demand for intraoperative fluids (3194 ml vs 1750 ml, P < 0.001). Most haemodynamic parameters did not differ significantly between high-dose POB pretreatment and low-dose POB pretreatment, but high-dose POB pretreatment was associated with a significantly higher intraoperative heart rate (120 +/- 19.5 vs 94 +/- 15.2 min(-1), P < 0.01). CONCLUSION: There is no significant difference in haemodynamic stability between MA and CA in phaeochromocytomas, but it is significantly inferior when compared to MA for cortical adenomas. We could not detect a beneficial effect of high-dose compared to low-dose POB pretreatment on intraoperative cardiovascular stability.

Adenoma↗
PubMed2006

Adrenocortical tumorigenesis.

Through the widespread use of imaging techniques with great sensitivity adrenal tumors are often diagnosed as an incidental finding. Although the majority of these adrenal lesions are benign and without evidence of endocrine activity or malignancy, hormone hypersecretion needs to be ruled out by specific tests. In addition to the classical forms of overt adrenocortical hypersecretion, it has become evident over the recent years that modest adrenocortical steroid autonomy as present in normokalemic primary aldosteronism and subclinical Cushing's syndrome is also associated with a significant morbidity. However, detection and differential diagnosis of these subtle changes in adrenal steroidogenesis can pose a diagnostic challenge to the clinician and is dependent on tests with reliable sensitivity and specificity. Regulation of adrenocortical development and growth, which results in clinical symptoms if disrupted, is dependent upon the distinct spatiotemporal expression of a variety of transcription factors as well as stimulation by extra-adrenal peptide hormones. Contributions to the elucidation of growth regulation of the adrenal cortex come from rare familiar syndromes associated with adrenocortical tumors, expression studies of adrenal tumor samples, in vitro studies on adrenocortical tumor cell lines, and mouse models displaying adrenal growth defects. In this review, we will summarize the important molecular aspects of adrenal tumorigenesis and highlight some prospects for clinical applications.

Adrenal Cortex↗
PubMed2006

Confirmatory testing in normokalaemic primary aldosteronism: the value of the saline infusion test and urinary aldosterone metabolites.

OBJECTIVE: Primary aldosteronism has recently been recognized as the most frequent cause of secondary hypertension. Since most patients are normokalaemic, differentiation to essential hypertension is challenging. As differentiation by baseline aldosterone/renin ratio may be insufficient, diagnosis should be confirmed by additional tests. However, as most confirmatory tests have been evaluated in hypokalaemic primary aldosteronism only, we reassessed the value of the saline infusion test and 24 h urinary aldosterone metabolites as confirmatory tests for both normo- and hypokalaemic primary aldosteronism under current antihypertensive medication. PATIENTS AND METHODS: 25 patients with primary aldosteronism (11 hypokalaemic, 14 normokalaemic), 29 patients with essential hypertension and 47 normotensive subjects were studied. The hypertensives received their usual medication with the exception of spironolactone. All subjects underwent a standard saline infusion test (determination of plasma aldosterone before and after 2.0 liters of isotonic saline for 4 hours i.v.) and collected a 24 h urine sample for examination of urinary tetrahydroaldosterone and aldosterone-18-glucuronide. RESULTS: In hypokalaemic primary aldosteronism the saline infusion test showed a reasonable sensitivity (91%) and specificity (90%). However, the test failed to differentiate sufficiently between essential hypertension and normokalaemic primary aldosteronism (sensitivity 57%, specificity 90%). Similarly, urinary tetrahydroaldosterone had higher sensitivity in hypokalaemic than in normokalaemic primary aldosteronism (sensitivity 64% vs 36%, specificity 100%), whereas for aldosterone-18-glucuronide, no differences in hypo- and normokalaemic primary aldosteronism were found (sensitivity 45% and 43%, specificity 100%). CONCLUSIONS: These data show that the saline infusion test as an established test in classical hypokalaemic primary aldosteronism is not a reliable test in the normokalaemic variant of the disease. Due to its low accuracy, determination of urinary aldosterone metabolites did not prove useful in confirming either normo- or hypokalaemic patients. We conclude from our data that these tests should not be used as confirmatory testing in the normokalaemic variant of primary aldosteronism.

Adult↗
PubMed2006

Gonadectomy in mice of the inbred strain CE/J induces proliferation of sub-capsular adrenal cells expressing gonadal marker genes.

Mouse models of adrenal tumorigenesis have the potential to give insights in the dysregulation of adrenal growth and differentiation. The inbred mouse strain CE/J has been reported to develop adrenal tumors upon gonadectomy (GDX) similar to mice with targeted deletions of the inhibin alpha subunit (Inh-/-). We performed a detailed morphological and molecular characterization of adrenal glands from CE/J mice 8-50 weeks of age to define the cellular origin of these tumors as well as the spatial and temporal expression of marker genes associated with tumor growth. In contrast to the induction of x-zone growth upon GDX in Inh-/- mice, GDX in CE/J mice induced the appearance of sub-capsular nests of densely packed cells that progress into adrenal tumors. Staining for proliferative cell nuclear antigen confirms a substantial increased in cellular proliferation within this sub-capsular compartment and lack of apoptosis upon GDX. Induction of adrenal tumor growth was accompanied by transcriptional changes that otherwise define gonadal endocrine cells. These regulated genes included transcription factors such as GATA-4, WT-1, FOG-1, and steroidogenic factor-1 (SF-1), peptide hormones such as Mullerian-inhibiting substance (MIS), hormone receptors including luteinizing hormone and MIS receptor, and steroidogenic enzymes such as P450c17 and P450 aromatase. The functional significance of steroid enzyme expression was demonstrated by a gradual increase of adrenal androgens after GDX. Taken together these data suggest that adrenal tumors in gonad-ectomized CE/J mice are direct derivatives from cells of the proposed sub-capsular stem cell zone. The distinct expression pattern of this cell population is consistent with a defect in the differentiation of these cells into a cell population with functional properties that otherwise define a gonadal endocrine phenotype.

Adrenal Gland Neoplasms↗
PubMed2005

Peroxisome proliferator-activated receptor-gamma agonists suppress adrenocortical tumor cell proliferation and induce differentiation.

CONTEXT: Thiazolidinediones (TZDs) have been implemented into clinical practice for the treatment of type 2 diabetes mellitus as specific peroxisome proliferator-activated receptor (PPAR)-gamma ligands. Moreover, recent evidence has suggested that TZDs might have favorable effects in the treatment of a variety of tumors as differentiation-inducing agents. Adrenocortical carcinoma (ACC) is a rare tumor entity with poor prognosis due to its highly malignant phenotype and lack of effective treatment options. OBJECTIVE: The purpose of this study was to investigate effects of TZDs on adrenocortical cancer cells. RESULTS: PPARgamma mRNA expression was detectable in all adrenocortical tumors including ACCs at similar levels. Furthermore, incubation of the adrenocortical tumor cell line NCI h295 with the PPARgamma agonist rosiglitazone led to a decrease in cell viability, a decrease of cellular proliferation, and an increase in apoptosis as well as steroidogenesis. On the molecular level, NCI h295 cells expressed higher levels of ACTH receptor (melanocortin receptor-2) mRNA upon treatment, whereas cyclin E mRNA was reduced, thus reflecting a shift toward an expression pattern found in less aggressive adrenocortical tumors in vivo. Accordingly, luciferase experiments confirmed an increased promoter activity for the melanocortin receptor-2 after stimulation with rosiglitazone. Coincubation with the specific PPARgamma antagonist GW9662 demonstrated the inhibition of TZD-induced increase in steroidogenesis, whereas growth suppression upon TZD treatment was not affected by GW9662. CONCLUSIONS: Thus, both PPARgamma-dependent and PPARgamma-independent effects of TZD treatment are likely to contribute to the observed phenotypical effects on NCI h295 cells. Taken together, these data indicate that TZDs might have the potential to become an additional treatment option as differentiation-inducing agents in patients with ACC.

Adrenal Cortex Neoplasms↗
PubMed2005

Clinical and molecular evidence for DAX-1 inhibition of steroidogenic factor-1-dependent ACTH receptor gene expression.

BACKGROUND: The ACTH receptor (ACTH-R) is a member of the seven transmembrane domain receptor super-family. In non-functional adrenal adenomas and adrenocortical carcinomas, ACTH-R expression is low. However, no inhibitory factor for ACTH-R expression has been defined to date. DAX-1 (dosage-sensitive sex reversal, adrenal hypoplasia congenita, critical region on the X chromosome, gene-1) is a general repressor of steroid production, inhibiting steroidogenic factor-1 (SF-1)-dependent expression of multiple steroidogenic enzymes. The aim of this study was to investigate whether ACTH-R gene transcription is affected by DAX-1 and whether this mechanism is involved in down-regulation of ACTH-R expression in adrenocortical tumors. METHODS: We screened 22 adrenocortical tumors for ACTH-R and DAX-1 mRNA expression by Northern blot. For in vitro analyses we co-transfected mouse Y1 adrenocortical carcinoma cells with the luciferase reporter gene vector pGL3 containing full-length constructs of human (h) or mouse (m) ACTH-R promoter together with a DAX-1 expression plasmid. These experiments were also performed using ACTH-R promoter 5'-deletion constructs and constructs mutated at the SF-1-binding sites. RESULTS: We found a negative correlation between DAX-1 and ACTH-R mRNA expression (R=-0.47, P<0.02). Accordingly, in vitro expression of DAX-1 significantly reduced hACTH-R and mACTH-R promoter activity by 89 and 55% respectively. DAX-1 inhibition was also present in the shortest construct of a series of 5'-deletion constructs of the human promoter extending from -64 to +40 bp relative to the transcription start site. Mutation of the SF-1-binding sites within the hACTH-R promoter resulted in reduced or abolished DAX-1 inhibition, arguing for a mechanism that involves SF-1 for DAX-1 inhibition. CONCLUSIONS: These data support the concept that DAX-1 is a major repressor of ACTH-R gene expression in vitro and in vivo.

Adenoma↗
PubMed2005

ACTH 1-24 inhibits proliferation of adrenocortical tumors in vivo.

OBJECTIVES: Although several lines of evidence suggest that the overall effects of the ACTH receptor, melanocortin 2 receptor (MC2-R), mediated signal transduction on adrenocortical growth and tumorigenesis are anti-proliferative, activation of MC2-R induces mitogens like jun, fos, and myc and activates the MAPK pathway. In vivo, potential effects of endogenous ACTH on adrenal tumori-genesis can not be separated from effects of other POMC derived peptides. METHODS: Murine adrenocortical tumor cells that lack MC2-R expression (Y6(pcDNA)) and Y6 cells stablely transfected with MC2-R (Y6(MC2-R)) were generated. Presence of functional MC2-R was demonstrated by RT-PCR and Western blot using an antibody for phosphorylated CREB. As a syngenic tumor model, LaHeF1/J mice simultaneously received 10(7) Y6(MC2-R) and Y6(pcDNA) subcutaneously, giving rise to MC2-R positive and negative tumors within the same animal. Animals were treated for 3 weeks in groups of 12 according to the following schedule: group A, control animals receiving saline injection; group B, animals receiving 5.7 ng/injection of a slow release formula of ACTH 1-24 administered i.p. three times a week (aiming at a low physiologic dose); and group C, animals receiving 57 ng/injection of ACTH 1-24 (high physiological dose). RESULTS: Twenty days of ACTH 1-24 treatment did not significantly affect corticosterone levels, endogenous ACTH levels or adrenal and thymus weight compared with saline injection. However, ACTH 1-24 treatment of group B and C mice significantly reduced tumor weight in MC2-R positive tumors in a dose dependent manner (P = 0.03), while no significant difference in tumor mass was observed in MC2-R negative tumors. PCNA and TUNEL staining, together with morphological characterization, demonstrated that these in vivo effects were due to reduced proliferation, while apoptosis and cellular hypertrophy within the tumor remained unchanged. CONCLUSION: MC2-R expression is associated with a less aggressive adrenal tumor phenotype and anti-proliferative effects can be amplified through stimulation with physiological doses of ACTH.

Adrenal Cortex Neoplasms↗
PubMed2005

Genetic influence of an ACTH receptor promoter polymorphism on adrenal androgen secretion.

OBJECTIVE: Adrenocorticotropic hormone (ACTH) is the primary secretagogue stimulating secretion of adrenal androgens (AA). Yet, genetic and environmental factors are assumed to play a determining role in the regulation of their biosynthesis and thus might explain the high variability of AA levels. Here we investigate the influence of an ACTH receptor promoter polymorphism affecting ACTH receptor gene transcription on ACTH-dependent dehydroepiandrosterone (DHEA) secretion. DESIGN: We recently reported a polymorphism within the transcription initiation site of the ACTH receptor gene promoter that alters the consensus sequence from CTC to CCC at -2 bp. This results in lower promoter activity in vitro and is associated with impaired cortisol response to ACTH stimulation in vivo. We now studied 14 normal, lean volunteers aged 20-35 years (eight CTC/CTC and six CCC/CCC carriers) in a 6-h ACTH stimulation test. METHODS: After overnight dexamethasone suppression, ACTH1-24 was administered continuously in each subject with hourly increasing doses (120-3840 ng/m2 body surface area/h) within a 6-h period. On a separate day, baseline DHEA samples were collected. RESULTS: In the 6-h ACTH stimulation test, CTC/CTC carriers showed a significantly higher DHEA response than CCC/CCC carriers (area under the curve: 19 367 +/- 2919 vs 11 098 +/- 1241 nmol/l per min; P < 0.04, Mann-Whitney U-test). In contrast, baseline DHEA concentrations did not differ between groups. CONCLUSION: These data demonstrate that genetic variations within the ACTH receptor promoter result in decreased DHEA secretion. Thus, we might have identified one of the genetic factors responsible for variation in ACTH-dependent DHEA secretion.

Adrenal Glands↗
PubMed2005

Sex-specific association of PTPN22 1858T with type 1 diabetes but not with Hashimoto's thyroiditis or Addison's disease in the German population.

BACKGROUND: Endocrine autoimmune disorders share genetic susceptibility loci, causing a disordered T-cell activation and homeostasis (HLA class II genes, CTLA-4). Recent studies showed a genetic variation within the PTPN22 gene to be an additional risk factor. MATERIALS AND METHODS: Patients with type 1 diabetes (n = 220), Hashimoto's thyroiditis (n = 94), Addison's disease (n = 121) and healthy controls (n = 239) were genotyped for the gene polymorphism PTPN22 1858 C/T. RESULTS: Our study confirms a significant association between allelic variation of the PTPN22 1858 C/T polymorphism and type 1 diabetes mellitus (T1D). 1858T was observed more frequently in T1D patients (19.3% vs 11.3%, P = 0.0009; odds ratio for allele T = 1.88, 95% confidence interval [1.3-2.7]). Furthermore, we found a strong association in female patients with T1D (P = 0.0003), whereas there was no significant difference between male patients with type 1 diabetes and male controls. No significant difference was observed between the distribution of PTPN22 C/T in patients with Hashimoto's thyroiditis or Addison's disease and healthy controls. CONCLUSION: The PTPN22 polymorphism 1858 C/T may be involved in the pathogenesis of type 1 diabetes mellitus by a sex-specific mechanism that contributes to susceptibility in females.

Addison Disease↗
PubMed2004

Rapid screening test for primary hyperaldosteronism: ratio of plasma aldosterone to renin concentration determined by fully automated chemiluminescence immunoassays.

BACKGROUND: The ratio of plasma aldosterone concentration to plasma renin activity (PAC/PRA) is the most common screening test for primary hyperaldosteronism (PHA), but it is not standardized among laboratories. We evaluated new automated assays for the simultaneous measurement of PAC and plasma renin concentration (PRC). METHODS: We studied 76 healthy normotensive volunteers and 28 patients with confirmed PHA. PAC and PRC were measured immunochemically in EDTA plasma on the Nichols Advantage chemiluminescence analyzer, and PRA was determined by an activity assay. RESULTS: In volunteers, PAC varied from 33.3 to 1930 pmol/L, PRA from 1.13 to 19.7 ng.mL(-1).h(-1) (0.215 ng.mL(-1).h(-1) = 1 pmol.L(-1).s(-1)), and PRC from 5.70 to 116 mU/L. PAC/PRA ratios ranged from 4.35 to 494 (pmol/L)/(ng.mL(-1).h(-1)) and PAC/PRC ratios from 0.69 to 71.0 pmol/mU. In PHA patients, PAC ranged from 158 to 5012 pmol/L, PRA from 0.40 to 1.70 ng.mL(-1).h(-1), and PRC from 0.80 to 11.7 mU/L. PAC/PRA ratios were between 298 and 6756 (pmol/L)/(ng.mL(-1).h(-1)) and PAC/PRC ratios between 105 and 2328 pmol/mU. Whereas PAC or PRC showed broad overlap between PHA patients and volunteers, the PAC/PRC ratio indicated distinct discrimination of these two groups at a cutoff of 71 pmol/mU. CONCLUSION: The PAC/PRC ratio offers several practical advantages compared with the PAC/PRA screening method. The present study offers preliminary evidence that it may be a useful screening test for PHA. Further studies are required to validate these results, especially in hypertensive cohorts.

Adolescent↗
PubMed2004

Striking complete remission after interferon-alpha for secondary recurrent non-Hodgkin's lymphoma but rare interferon-induced side effects.

Interferon (IFN) treatment is a therapeutic option in the treatment of non-Hodgkin's lymphoma (NHL). Although randomized trials have failed to show significant differences in progression-free and overall survival (OS) with IFN compared to placebo after peripheral blood stem cell transplantation (PBSCT) as well as standard therapy for NHL, anecdotal case reports have documented impressive results in selected patients. With this case report, we demonstrate an astounding success of IFN therapy given in the treatment of a young man with second relapse after two consecutive autologous PBSCTs and abdominal irradiation. With occurrence of multiple lymph node enlargements despite this intensive treatment, he received IFN and obtained a well-documented complete remission (CR). Yet, treatment with IFN always has to be considered in the context of its significant side effect profile, which can have considerable impact on the patient's quality of life as illustrated in this case report.

Drug Evaluation↗
PubMed2004

Steroidogenic acute regulatory (StAR)-directed immunotherapy protects against tumor growth of StAR-expressing Sp2-0 cells in a rodent adrenocortical carcinoma model.

Adrenocortical carcinoma (ACC) is a highly malignant tumor with poor response to classical antitumor therapy. Steroidogenic acute regulatory (StAR) protein is expressed in most human ACCs. The aim of this study was to induce antitumoral T cells directed against StAR in a murine tumor model. Because a suitable syngenic adrenocortical mouse tumor model is lacking, we established a clone of the mouse myeloma Sp2-0 tumor cell line stably expressing murine StAR (Sp2-mStAR). Using repeated im injections of plasmid DNA encoding mStAR followed by infection with a recombinant vaccinia virus (rVV) expressing mStAR, we induced a cytotoxic T-cell response as measured by enzyme-linked immunospot assay. To demonstrate antitumor activity of the vaccination procedure, mice were treated as follows: group A, mice immunized with plasmids and rVV encoding mStAR receiving Sp2-mStAR cells; control group B, mice immunized with the empty plasmid and the empty rVV receiving Sp2-mStAR cells; control group C, mice immunized with the empty plasmid and rVV encoding P450 side-chain cleavage enzyme receiving Sp2-mStAR cells; and control group D, mice immunized with plasmid and rVV encoding mStAR receiving parental Sp2-0 cells. A high proportion (89-100%) of the control groups B, C, and D developed subcutaneous tumors. In contrast, immunization specific for mStAR (group A) was highly protective against tumor growth (percentage of tumor-free animals, 67%; P < 0.001 vs. controls). In summary, these results show that T-cell tolerance toward mStAR can be broken, resulting in antitumoral immunity. Thus, StAR represents a candidate target antigen for immunotherapeutic strategies against ACC.

Adrenal Cortex Neoplasms↗