Insulin-like growth factor-I (IGF-I) plasma concentrations are increased in depressed patients

There is some evidence that the somatotrophic system in depression, as assessed by basal growth hormone (GH) concentrations and by GH releasing hormone (GHRH) challenge, might be dysfunctional. However, the rather limited data have been inconclusive so far and plasma concentrations of both insulin-like growth factor-1 (IGF-I) and binding proteins (IGFBP 1 to IGFBP-6) have not been measured simultaneously in depressed patients. We studied 24 severely depressed patients and 33 healthy controls and estimated 24-hour mean plasma cortisol, six-hour evening mean plasma growth hormone (GH), morning plasma IGF-I, IGFBP 2 and 3 and GH-binding protein (GH-BP). Twenty-four-hour mean cortisol (306 +/- 69 vs. 196 +/- 30 nmol/l, p < .001) and IGF-I (157 +/- 40 vs. 120 +/- 33 micrograms/l, p < .01) plasma concentrations were found to be significantly increased in depressed patients, while there was no difference in GH or binding proteins between both groups. MANOVA analysis revealed age and diagnosis to have main effects upon plasma IGF-I. Especially young age and a diagnosis of major depression are associated with higher plasma IGF-I. After treatment only patients in remission had attenuated IGF-I plasma concentrations. We conclude that plasma IGF-I is increased in acutely depressed patients similar to other states of hypercortisolemia.     

Hypothalamic-pituitary-adrenal axis function and platelet serotonin concentrations in depressed patients

Plasma cortisol and platelet serotonin (5-hydroxytryptamine, 5-HT) concentrations were determined in 39 male psychotic and 39 male non-psychotic depressed inpatients, and in 69 male healthy control subjects. Psychotic or non-psychotic depressed patients had higher predexamethasone plasma cortisol levels than found in the control group. After the dexamethasone suppression test (DST), psychotic and non-psychotic depressed patients were subdivided into suppressors and non-suppressors. Psychotic and non-psychotic patients had significantly different platelet 5-HT concentrations among themselves and compared with the control group. However, there was no significant correlation between plasma cortisol levels and platelet 5-HT concentrations. Dexamethasone administration did not affect platelet 5-HT concentrations within subtypes of depressed patients. Abnormal cortisol suppression after the DST occurred more frequently in psychotic than in non-psychotic patients. Platelet 5-HT and plasma cortisol concentrations were decreased in patients with pronounced suicidal behaviour. Our results suggest that plasma cortisol and platelet 5-HT concentrations might serve as independent biological markers for different subtypes of depression.     

Increased plasma atrial natriuretic peptide and endothelin concentrations after surgery in patients with esophageal and gastric cancer

Endothelin-1 (ET-1) and human atrial natriuretic peptide (hANP) are known as vasoactive substances. In the present study, an attempt was made to evaluate the mode by which these substances are secreted in patients having severe surgical stress. Plasma ET-1 and hANP concentrations were measured in 15 patients with esophageal carcinoma who underwent subtotal esophagectomy via right-thoraco-ventrotomy (EC group) and 10 patients with gastric carcinoma who underwent total gastrectomy via ventrotomy (GC group). The volume of intraoperative hemorrhage was significantly larger and operation time was significantly longer in the EC group than in the GC group. Plasma ET-1 concentration in the EC group increased remarkably on the first operative day (1st POD), whereas that in the GC group did not. Plasma levels of hANP in both the EC and GC groups gradually increased until they peaked on the 2nd POD. The increment of plasma hANP secretion for the EC group was significantly higher than that for the GC group on the day of the operation, suggesting that ET-1 stimulated hANP in the EC group. Plasma hANP levels reached their peak values on the 2nd POD and returned to the preoperation level on the 5th POD, while PCWP did not change significantly after the surgery. Since this discrepancy between the postoperation patterns of PCWP and hANP cannot be explained by changes in the circulating blood volume, hANP secretion may be regulated by certain factors in addition to the left ventricular pressure experienced by patients receiving heavy operation stress, such as those in the EC group.     

Increased serum IgD concentrations in patients with Hodgkin's disease

Serum IgD concentrations have been determined in twenty-one patients with Hodgkin's disease, in eight patients with non-Hodgkin's lymphomas and in twenty-eight normal (control) individuals by both a solidphase radio-immuno-assay and radial-immunodiffusion. Fourteen of the Hodgkin's patients displayed three to forty-five-fold increased serum IgD levels as compared to control individuals, while in the remaining seven patients IgD concentrations were practically normal. Patients with non-Hodgkin's lymphomas had decreased IgD concentrations.     

Neuroactive steroid concentrations following metyrapone administration in depressed patients and healthy volunteers

BACKGROUND: There is evidence that treatment with the 11 beta-hydroxylase inhibitor metyrapone may represent an alternative treatment strategy in major depression. As a consequence of inhibition of cortisol synthesis the overdrive of corticotropin leads to an accumulation of precursor steroids. However, the effects of metyrapone on the concentrations of endogenous neuroactive steroids that modulate ion channels, e.g., the GABAA receptor, have not yet been studied systematically. METHODS: Therefore, we quantified the concentrations of an array of neuroactive steroids following administration of 1.5 g metyrapone before and after pretreatment with 1 mg dexamethasone in 19 patients suffering from severe depression in comparison to 13 healthy controls by means of a highly sensitive gas chromatography/mass spectrometry analysis. RESULTS: The administration of metyrapone induced a pronounced increase in all neuroactive steroids studied both in patients and controls that was prevented by dexamethasone pretreatment. CONCLUSIONS: Thus, the psychotropic properties of endogenous neuroactive steroids may contribute to the antidepressant properties of metyrapone in the treatment of major depression.     

Increased serum concentrations of interleukin-10 in patients with hepatosplenic candidiasis

Hepatosplenic candidiasis (HSC) becomes clinically overt in cancer patients upon recovery from neutropenia. HSC may be a consequence of a Th1-Th2 imbalance, characterized by increased serum levels of one or more cytokines. Serum levels of two immunosuppressive cytokines, markers of the Th2 pathway, interleukin (IL)-4 and IL-10 were measured by ELISA in 10 patients with HSC (22 samples) and compared with 19 healthy blood donors, 13 patients with cancer but no infection (23 samples), and 11 patients with cancer and various bacterial infections (17 samples). IL-4 was undetectable in all controls and patients. By contrast, levels of IL-10 were increased in HSC patients compared with levels in healthy donors and cancer patients without infection (P < .001) or with bacterial infections (P < .01). These findings indicate that IL-10 but not IL-4 is increased in patients with HSC and suggest that IL-10 plays a role in the pathogenesis of this infection.     

Increased plasma concentration of adrenomedullin in patients with subarachnoid hemorrhage

Adrenomedullin (AM) is a potent hypotensive peptide originally identified in pheochromocytoma tissues. Impaired cardiovascular conditions, such as hypertension, myocardial infarction, and septic shock, stimulate production of AM. This study was performed to determine whether subarachnoid hemorrhage (SAH) altered plasma AM concentration. Plasma concentrations of AM in 17 patients with SAH were measured for 2 wk after the onset of SAH by AM-specific radioimmunoassay. Plasma concentrations of AM were increased in patients with SAH throughout the study period, compared with those in control subjects. Plasma concentrations of AM in patients classified as Hunt and Kosnik grade III or IV were significantly higher than those classified as Hunt and Kosnik grade I or II on the day of and the day after the onset of SAH. However, plasma concentrations of AM were unaffected by angiographic vasospasm. These findings suggest that plasma concentrations of AM are increased in patients with SAH and may reflect the severity of SAH. IMPLICATIONS: Adrenomedullin has been reported to affect the cerebral circulation. This study was performed to determine whether subarachnoid hemorrhage, a typical cerebrovascular disorder, altered plasma adrenomedullin concentrations. We found that plasma adrenomedullin concentrations increased in patients with subarachnoid hemorrhage, although no relationship was found between plasma adrenomedullin concentration and angiographic vasospasm. Plasma adrenomedullin concentration may reflect the severity of hemorrhage.     

Increased plasma endothelin-1 concentrations in E. coli septic peritonitis rats with diabetes mellitus

To study the diabetic mellitus (DM) patient's reaction to sepsis, we investigated the survival rate, the bacteremia, plasma endotoxin and plasma endothelin-1 levels in E. coli septic peritonitis rats with or without streptozotocin-induced DM. No significant difference could be detected between the DM and nondiabetic rats in the survival rate, the bacteremia level or the plasma endotoxin level. The DM rat manifested a significant increase compared to the nondiabetic rat in the plasma endothelin-1 level four hours after the outbreak of peritonitis. Endothelin-1 may thus play some role in the E. coli septic peritonitis rat with DM.     

Serum dehydroepiandrosterone sulfate and androstenedione concentrations in children with adrenal disorders

Although lung transplantation is considered a definitive treatment of patients with advanced pulmonary vascular disease and pulmonary hypertension, advances in the success of the medical management of patients with pulmonary hypertension make it less clear as to when to refer a patient for transplantation. Coumadin anticoagulation is associated with improved survival in all patients, and calcium channel blockers therapy with improved survival in very select patients. Chronic prostacyclin represents a newer therapy that seems to have a dramatic impact on patients' functional class and survival. As improvements continue in the medical management in pulmonary hypertension, and in survival of patients undergoing lung transplantation, the guidelines for patient selection should be constantly evolving.     

Increased levels of plasma cholesteryl ester hydroperoxides in patients with subarachnoid hemorrhage

The pathophysiology of subarachnoid hemorrhage (SAH) may involve free radical production and lipid peroxidation. We examined plasma levels of cholesteryl ester hydroperoxides (CEOOH) and antioxidants in 25 patients with SAH, and 10 neurologic controls with lacunar stroke. Patients with SAH had significantly increased plasma levels of CEOOH, which peaked on day 5 after the ictus. Concentrations of CEOOH were significantly increased, and ascorbic acid concentrations were significantly decreased in patients who developed vasospasm compared with patients without vasospasm. Increased levels of CEOOH were associated with increased mortality and correlated with clinical outcome scales. These results implicate oxidative stress in the pathogenesis of SAH and suggest that measurements of CEOOH in plasma may be useful both prognostically as well as in monitoring therapeutic interventions.     

Elevated platelet factor 4 and beta-thromboglobulin plasma levels in depressed patients with ischemic heart disease

Clinical depression has recently been recognized as an independent risk factor for cardiac mortality in patients after myocardial infarction. The underlying mechanisms of this increased mortality remain unclear. This study investigated the hypothesis that patients suffering from ischemic heart disease (IHD) and depression concurrently may have abnormal platelet activation resulting in an increased risk of thrombosis. Platelet factor 4 (PF4) and beta-thromboglobulin (beta-TG) were measured in young healthy control subjects, in nondepressed patients with IHD, and in depressed patients with IHD. Mean PF4 and beta-TG plasma levels in the IHD group with depression were found to be significantly higher than those of the control and IHD groups. This increase was not related to age, gender, racial difference, aspirin use, or severity of cardiac disease. This finding suggests that in depressed patients with IHD there is greater platelet activation, and may indicate an increased risk of thrombotic complications.     

Increased brain natriuretic peptide and atrial natriuretic peptide plasma concentrations in dialysis-dependent chronic renal failure and in patients with elevated left ventricular filling pressure

Brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) plasma concentrations were measured in patients with dialysis-dependent chronic renal failure and in patients with coronary artery disease exhibiting normal or elevated left ventricular end-diastolic pressure (LVEDP) (n = 30 each). Blood samples were obtained from the arterial line of the arteriovenous shunt before, 2 h after the beginning of, and at the end of hemodialysis in patients with chronic renal failure. In patients with coronary artery disease arterial blood samples were collected during cardiac catheterization. BNP and ANP concentrations were determined by radioimmunoassay after Sep Pak C18 extraction. BNP and ANP concentrations decreased significantly (P < 0.001) during hemodialysis (BNP: 192.1 +/- 24.9, 178.6 +/- 23.0, 167.2 +/- 21.8 pg/ml; ANP: 240.2 +/- 28.7, 166.7 +/- 21.3, 133.0 +/- 15.5 pg/ml). The decrease in BNP plasma concentrations, however, was less marked than that in ANP plasma levels (BNP 13.5 +/- 1.8%, ANP 40.2 +/- 3.5%; P < 0.001). Plasma BNP and ANP concentrations were 10.7 +/- 1.0 and 60.3 +/- 4.0 pg/ml in patients with normal LVEDP and 31.7 +/- 3.6 and 118.3 +/- 9.4 pg/ml in patients with elevated LVEDP. These data demonstrate that BNP and ANP levels are strongly elevated in patients with dialysis-dependent chronic renal failure compared to patients with normal LVEDP (BNP 15.6-fold, ANP 2.2-fold, after hemodialysis; P < 0.001) or elevated LVEDP (BNP 6.1-fold, ANP 2.0-fold, before hemodialysis; P < 0.001), and that the elevation in BNP concentrations was more pronounced than that in ANP plasma concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)     

Increased heart rate in depressed subjects in spite of unchanged autonomic balance?

A clinical study was conducted to examine the effects of depression on cardiac autonomic control. Cardiac autonomic control was measured in 26 nonmedicated patients (19 females) suffering from Major Depression, melancholic type, and in 26 age- and sex-matched normal controls. We measured heart rate and high frequency heart rate variability (respiratory sinus arrhythmia), pulsewave velocity and blood pressure, during 10 min of supine rest under controlled conditions. Using a log transformed time domain measure of respiratory sinus arrhythmia (logRSA), we found an inverse linear dependence between cardiac vagal tone and age in the healthy subjects as well as the depressed patients. logRSA was 0.22+/-0.25 in the patients and 0.25+/-0.16 in the control group. While this difference was not significant (P > 0.1), the deviations from the regression line were significantly (P < 0.0005) greater in the patients (0.21+/-0.12) than in the control group (0.09+/-0.07), indicating a more heterogeneous vagal tone in the depressed patients. Heart rate was also significantly (P < 0.03) greater in the depressed patients (76.6+/-12.4) than in the control group (69.5+/-6.9). No between-group differences were found in pulsewave velocity or systolic blood pressure, but diastolic blood pressure was lower in depressed patients (73.5+/-8.7 vs. 80.8+/-9.1). We discuss the possibility that the increased heart rate seen in the absence of vagal tone changes may not be due to altered vagal or sympathetic tone, as measured in this study. Other factors, including altered autonomous heart rate, may be responsible for the higher heart rate in the depressed group.     

Short-term outcomes of detected and undetected depressed primary care patients and depressed psychiatric patients

The aims of this study were to determine whether detection of major depression in primary care was associated with improved outcome, and to compare the 4.5 month outcomes of detected and undetected depressed primary care patients and depressed psychiatric patients. Primary care patients with major depression were recruited from the practices of 50 family physicians in Southeastern Michigan using a two-stage selection procedure employing the Center for Epidemiologic Studies-Depression Scale (CES-D) and the Structured Clinical Interview for DSM-III-R (SCID); clinician detection of depression was ascertained by response to a direct query on a rating form. Depressed patients seeking treatment in an outpatient psychiatric setting also received the CES-D and the SCID. Data on patient demographics and clinical characteristics were obtained for both primary care and psychiatric patients. Initial and 4.5 month scores on the Hamilton Depression Rating Scale (HAM-D) were obtained for 34 undetected and 25 detected depressed primary care and 55 depressed psychiatric patients. Improvement in depression over time was assessed by the change in HAM-D scores over the 4.5 months. The three groups did not differ in initial severity. Both psychiatric and undetected primary care patients showed significant improvement at 4.5 months, whereas detected primary care patients did not improve. At 4.5 months there were no differences in mean HAM-D scores between undetected, depressed primary care patients and depressed psychiatric outpatients. This result did not change after controlling for age and severity of depression at initial presentation, nor did it change after exclusion of cases of mild depression to control for a possible "floor effect." However, differences among groups in the stage of depressive episodes may have affected this comparison. These findings suggest that an exclusive focus on increasing detection of depression in primary care patients is unlikely to improve outcomes, and that undetected depression among primary care patients does not necessarily represent poor quality of care. Although depressed psychiatric patients in this study had better outcomes than detected depressed primary care patients, the presence of unmeasured differences among groups in the stage of the depressive episode makes it impossible to determine whether treatment of depression by psychiatrists is superior to that provided by primary care physicians. These findings should stimulate efforts to examine a more comprehensive model for detection and treatment of depression in primary care.     

Increased plasma concentrations of serum amyloid A: an indicator of the acute-phase response after cardiopulmonary bypass

OBJECTIVES: To assess the expression of mixed and hepatic venous serum amyloid A (SAA) concentrations and its relationship to plasma concentrations of C-reactive protein, interleukin-6 (IL-6), and endotoxin during and after cardiopulmonary bypass (CPB). DESIGN: Prospective, consecutive sample with repeated measurements. SETTING: Surgical intensive care unit (ICU) in a university hospital. PATIENTS: Twenty patients who underwent elective coronary bypass grafting. INTERVENTIONS: A radial artery catheter, pulmonary artery catheter, and right hepatic vein catheter were inserted. Blood samples were collected to determine the different mediators, lactate concentrations, and oxygen saturations. MEASUREMENTS AND MAIN RESULTS: After induction of anesthesia, baseline values were obtained and the following parameters were determined 20 mins after onset of CPB, 20 mins after termination of CPB, at admission to the ICU, and 6, 8, 12, and 24 hrs later: hemodynamics, body core temperature, hepatic venous oxygen saturation, and mixed and hepatic venous lactate, endotoxin, interleukin (IL)-6, C-reactive protein (CRP), and SAA concentrations. Endotoxin and IL-6 plasma concentrations increased during CPB, peaked 6 hrs after admission to the ICU (endotoxin: 23.1 +/- 6.2 pg/mL; IL-6: 646 +/- 104 pg/mL), and decreased thereafter; SAA and CRP concentrations began to increase after 6 and 8 hrs, respectively, with the highest concentrations reached 24 hrs postoperatively (CRP: 14 +/- 3.6 mg/L; SAA: 668 +/- 114 micrograms/mL). Lactate concentrations began to increase 20 mins after CPB, and continued to increase until 12 hrs postoperatively. There were no significant differences between mixed and hepatic venous values of endotoxin, IL-6, CRP, SAA, and lactate (p < .05). Body core temperature, which was < 37.5 degrees C before surgery for all patients, increased 6 hrs after admission to the ICU and peaked 12 hrs postoperatively (38.3 +/- 1.1 degrees C). Hepatic venous oxygen saturation did not change. Correlations were obtained between IL-6 values and heart rate (r2 = .20; p < .005), and endotoxin concentrations and systemic vascular resistance (r2 = .18; p < .001). Body core temperature correlated significantly closer with SAA (r2 = .52; p < .0001) values than with IL-6 (r2 = .27; p < .0001) or CRP (r2 = .16; p < .001) values (p < .05). CONCLUSIONS: SAA is an additional and sensitive marker of the acute-phase response following CPB; the increase in SAA concentrations parallels the temporary increase in body core temperature and is preceded by endotoxemia and IL-6 secretion.     

Calcium alpha-ketoglutarate administration to malnourished hemodialysis patients improves plasma arginine concentrations

Calcium alpha-ketoglutarate administration to 24 malnourished hemodialysis patients for 1 year leads to a significant increase in plasma concentrations of L-arginine from 53.6 +/- 18.3 (compared to a healthy control group: 87.5 +/- 27.3) to 71.1 +/- 15.9 mumol/l (p < 0.05). Furthermore, concentrations in plasma of proline and histidine, precursors of glutamate biosynthesis, are increased; inorganic phosphate and urea are significantly decreased in hemodialysis patients after 1 year of calcium alpha-ketoglutarate administration.