Circulating natriuretic peptide concentrations in patients with end-stage renal disease: role of brain natriuretic peptide as a biomarker for ventricular remodeling.

OBJECTIVES: To determine levels of natriuretic peptides (NPs) in patients with end-stage renal disease (ESRD) and to examine the relationship of these cardiovascular peptides to left ventricular hypertrophy (LVH) and to cardiac mortality. PATIENTS AND METHODS: One hundred twelve dialysis patients without clinical evidence of congestive heart failure underwent plasma measurement of NP concentrations and echocardiographic investigation for left ventricular mass index (LVMI). RESULTS: Plasma atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) concentrations correlated positively with LVMI and inversely with left ventricular ejection fraction, whereas C-type NP and Dendroaspis NP levels did not correlate with LVMI. In dialysis patients with LVH (LVMI >125 g/m2), plasma ANP and BNP concentrations were increased compared with those in dialysis patients without LVH (both P<001). In a subset of 15 dialysis patients without LVH or other concomitant diseases, plasma BNP concentrations were not significantly increased compared with those in 35 controls (mean +/- SD, 20.1+/-13.4 vs 13.5+/-9.6 pg/mL; P=.06), demonstrating that the BNP concentration was not increased by renal dysfunction alone. Furthermore, the BNP level was significantly higher in the 16 patients who died from cardiovascular causes compared with survivors (mean +/- SD, 129+/-13 vs 57+/-7 pg/mL; P<.003) and was significantly associated with greater risk of cardiovascular death in Cox regression analysis (P<.001), as was the ANP level (P=.002). CONCLUSIONS: Elevation of the plasma BNP concentration is more specifically related to LVH compared with the other NP levels in patients with ESRD independent of congestive heart failure. Thus, BNP serves as an important plasma biomarker for ventricular hypertrophy in dialysis patients with ESRD.

Long-term outcome of panic disorder with agoraphobia treated by exposure.

BACKGROUND: There is a paucity of long-term outcome studies of panic disorder that exceed a 2-year follow-up. The aim of the study was to evaluate the long-term follow-up of patients with panic disorder with agoraphobia treated according to a standardized protocol. METHODS: A consecutive series of 200 patients satisfying the DSM-IV criteria for panic disorder with agoraphobia was treated in an out-patient clinic with behavioural methods based on exposure homework. One hundred and thirty-six patients became panic free after 12 sessions of psychotherapy and 132 were available for follow-up. A 2- to 14-year (median = 8 years) follow-up was performed. Survival analysis was employed to characterize the clinical course of patients. RESULTS: Thirty-one of the 132 patients (23%) had a relapse of panic disorder at some time during follow-up. The estimated cumulative percentage of patients remaining in remission was 93.1 after 2 years, 82.4 after 5 years, 78.8 after 7 years and 62.1 after 10 years. Such probabilities increased with younger age, and in the absence of a personality disorder, of high pre-treatment levels of depressed mood, of residual agoraphobic avoidance after exposure, and of concurrent use of benzodiazepines and antidepressant drugs. CONCLUSIONS: The findings suggest that exposure treatment can provide lasting relief to the majority of patients with panic disorder and agoraphobia. Disappearance of residual and subclinical agoraphobic avoidance, and not simply of panic attacks, should be the aim of exposure therapy.

Long-term outcome of social phobia treated by exposure.

BACKGROUND: There is very little information on long-term follow-up of social phobia. METHODS: A consecutive series of 70 patients satisfying the DSM-IV criteria for social phobia was treated in an out-patient clinic with behavioural methods based on exposure homework. Forty-five patients were judged to be remitted after eight individual sessions of psychotherapy. A 2 to 12 year (median = 6 years) follow-up was performed. Survival analysis was selected to characterize the clinical course of patients. Assessments were performed before treatment, at the end of therapy, after 1 year, and subsequently on a yearly basis, and utilized selected items of Paykel's Clinical Interview for Depression. RESULTS: Six of the 45 patients (13%) had a relapse of social phobia at some time during follow-up. The estimated cumulative percentage of patients remaining in remission was 98 after 2 years, 85 after 5 years and 85 after 10 years. Such probabilities increased in the absence of a personality disorder, of residual social phobic avoidance after exposure, and of concurrent use of benzodiazepines. CONCLUSIONS: The findings suggest that, even though one patient out of three is unable to complete treatment or does not benefit sufficiently from it, exposure treatment can provide lasting effects to the majority of patients with social phobia. Disappearance of residual, subclinical social phobic avoidance appears to be the target of treatment.

Effect of the serotonin antagonists ritanserin and ketanserin in Cushing's disease.

Central serotonergic regulation could have a role in the course of pituitary-dependent Cushing's disease. We studied the effects of ritanserin and ketanserin, two related selective 5HT2 receptor antagonists, in 11 patients with Cushing's disease. Treatment lasted from 1 month to 1 year (up to 4 years in one patient). Daily doses were 10-15 mg for ritanserin, and 40-80 mg for ketanserin. Since the two drugs share the same mechanism of action and no qualitative or quantitative differences in response to their administration were observed, the results were pooled together. Patients were assessed by clinical and hormonal evaluation. Urinary cortisol and ACTH were considered the parameters of interest. Short-term response: after 1 month, there was a significant decrease of urinary cortisol from 781 (160) to 331 (215) nmol/d (P < 0.02) while ACTH was 9.8 (1.5) pmol/L baseline and again 8.8 (2.2) pmol/L at 1 month (P = NS). For 9 patients, hormonal parameters were available after 1 week of treatment. In this case, also ACTH levels were significantly decreased (from 9.6 (1.7) to 5.2 (1.3) pmol/L; P < 0.01) together with urinary cortisol (from 781 (194) to 372 (165) nmol/d; P < 0.01). Long-term response: in 3 patients, hormonal parameters failed to respond to serotonin receptor antagonists, which were thus discontinued. An improvement was recorded in the remaining 8 patients, that was prolonged in 3, and transient in 5. In 3 of these latter patients, a marked increase of ACTH was observed before treatment discontinuation. Ketanserin was given to 2 patients with Nelson's syndrome, with only transient ACTH decrease in one, and no changes in ACTH response to CRH after 1 month treatment in both cases. An inhibitory effect of ritanserin and ketanserin on ACTH and cortisol production in Cushing's disease appeared to be limited both in terms of duration of response and number of patients with a satisfactory outcome. However, the results may provide a better understanding of serotonergic modulation in Cushing's disease and lead to therapeutic developments.

Prevention of recurrent depression with cognitive behavioral therapy: preliminary findings.

BACKGROUND: Cognitive behavioral treatment (CBT) of residual symptoms after successful pharmacotherapy yielded a substantially lower relapse rate than did clinical management in patients with primary major depressive disorders. The aim of this study was to test the effectiveness of this approach in patients with recurrent depression (> or = 3 episodes of depression). METHODS: Forty patients with recurrent major depression who had been successfully treated with antidepressant drugs were randomly assigned to either CBT of residual symptoms (supplemented by lifestyle modification and well-being therapy) or clinical management. In both groups, during the 20-week experiment, antidepressant drug administration was tapered and discontinued. Residual symptoms were measured with a modified version of the Paykel Clinical Interview for Depression. Two-year follow-up was undertaken, during which no antidepressant drugs were used unless a relapse ensued. RESULTS: The CBT group had a significantly lower level of residual symptoms after discontinuation of drug therapy compared with the clinical management group. At 2-year follow-up, CBT also resulted in a lower relapse rate (25%) than did clinical management (80%). This difference attained statistical significance by survival analysis. CONCLUSIONS: These results challenge the assumption that long-term drug treatment is the only tool to prevent relapse in patients with recurrent depression. Although maintenance pharmacotherapy seems to be necessary in some patients, CBT offers a viable alternative for other patients. Amelioration of residual symptoms may reduce the risk of relapse in depressed patients by affecting the progression of residual symptoms to prodromes of relapse.

Hypochondriacal fears and beliefs in obsessive-compulsive disorder.

The relationship of obsessions and compulsions with hypochondriasis is receiving increasing attention, but has not been substantiated by adequate research. The Illness Attitude Scales (IAS), which identify hypochondriacal patients, were administered to 30 patients with DSM-IV obsessive-compulsive disorder and 30 healthy control subjects matched for sociodemographic variables. All IAS scales were significantly higher in patients with obsessions and compulsions. However, there were no significant differences between patients and controls in the number of subjects whose symptom intensity exceeded a clinical threshold for hypochondriasis and disease phobia. Furthermore, hypochondriacal fears and beliefs were poorly correlated with obsessions and compulsions. The results suggest the presence of mild abnormal illness behaviour in patients with obsessive-compulsive disorder, unlike the situation in patients with panic disorder and depression.

Benzodiazepines and anxiety sensitivity in panic disorder.

1. Benzodiazepines were discontinued in 16 patients who had recovered from panic disorder with agoraphobia after exposure treatment. 2. Drug discontinuation yielded a significant decrease in anxiety sensitivity and state anxiety in these long-term users. 3. Several likely explanations for the findings are discussed. 4. In the short term, treatment of panic disorder with benzodiazepines may lower anxiety symptoms. However, in the long run, it may decrease the individual tolerance to anxiety and discomfort.

Patterns of ACTH response to oCRH in Cushing's disease: correlation with histological/immunocytochemical findings.

The most common lesion in Cushing's disease is an anterior pituitary adenoma. However, normal or hyperplastic corticotropic pituitary tissue has also been found in some cases. In an attempt to distinguish the patterns of ACTH response to oCRH in different forms of anterior pituitary hypersecretion, 17 patients with pituitary adenoma and 17 without pathological evidence of adenoma were studied. These patients underwent transsphenoidal pituitary surgery by the same surgeon and were retrospectively evaluated. The diagnosis of pituitary lesions was confirmed by microscopical and immunohistochemical studies. Patients without pituitary adenoma showed a higher and more prolonged mean plasma ACTH response than that observed in patients with pituitary tumors. In patients with pituitary adenoma, the peak ACTH response was observed within 30 min after oCRH administration, and was followed by a gradual decrease to basal levels in the following 30 min. In those cases in whom no pituitary adenoma was found, oCRH injection produced a marked increase in plasma ACTH levels during the first 60 min with a slower decline at the subsequent time points. The mean response curves of the two groups, analyzed by Beherens-Fischer nonparametric ANOVA, showed significant differences, either when they were compared globally (p < 0.01), or at single time points. Differences in ACTH response to oCRH stimulation support the hypothesis of different pathogenetic mechanisms leading to ACTH hypersecretion in Cushing's disease with and without pituitary adenoma.

A local renin-angiotensin system in the human adrenal gland: evaluation of in vitro secretion by a non-parametric combination of randomness permutation tests.

The aim of this study is to assess the mode of release of renin, angiotensin II and aldosterone during in vitro superfusion of the human adrenal gland using a non-parametric combination of four randomness tests. Five normal adrenals and four aldosteronomas superfused over 270 mins were found to concomitantly release renin, angiotensin II and aldosterone. The pattern of this release exhibited a significantly non-random pulsatile character in 17 out of 23 single hormone series (p < 0.05). A further statistical combination-test analyzing the release of each hormone for all experiments with normal and pathological tissue, respectively, showed significant pulsatility (p < 0.01) in 5 out of 6 groups. The pulsatile mode of in vitro hormone release by the human adrenals indicates an active secretory process rather than a discharge of tissue-stored forms. The source of such intra-adrenal intrinsic pulse-generating mechanism could reflect the periodic course of a negative biological feedback reaction.

Neurocirculatory asthenia: a reassessment using modern psychosomatic criteria.

The purpose of this study was to assess the prevalence of mental illness and to evaluate the quality of life of patients with neurocirculatory asthenia. A consecutive series of 80 patients who satisfied the diagnostic criteria developed by Kannel et al. for neurocirculatory asthenia was included in this study. Patients underwent a psychiatric diagnostic research interview and extensive psychometric evaluation, with both observer and self-rated scales for depression, anxiety, phobic symptoms, quality of life and abnormal illness behavior. In 47 patients (59%), a psychiatric diagnosis (mainly an anxiety disorder) antedated the onset of neurocirculatory asthenia, which was thus defined as secondary, also because cardiorespiratory symptoms were part of the mental symptoms. In the remaining 33 patients (41%) neurocirculatory asthenia was the primary disorder. Patients with secondary neurocirculatory asthenia reported significantly higher levels of anxiety, depression, social phobia, abnormal illness behavior and an impaired quality of life compared with patients with primary neurocirculatory asthenia. This latter did not significantly differ in these variables (except for depression) from healthy control subjects matched for sociodemographic variables. At a 1-year follow-up, patients with primary neurocirculatory asthenia had a much better prognosis than those with secondary neurocirculatory asthenia. The results indicate the feasibility of the primary/secondary distinction based on the time of onset of mental and cardiorespiratory symptoms in neurocirculatory asthenia. Since only about one quarter of the patients were found to suffer from decreased energy and fatigue according to specified criteria, the terms neurocirculatory asthenia and effort syndrome should probably be discarded.

Quality of life of hirsute women.

Hirsutism is recognized to cause profound distress in affected women, due to cosmetic and psychosexual implications. It was evaluated in the present study by methods found to be valid and reliable in psychosomatic research. Fifty women with hirsutism belonging to the spectrum of disorders from idiopathic hirsutism to polycystic ovary syndrome, after complete medical work-up, underwent the same psychometric evaluation as 50 healthy non-hirsute women, matched for sociodemographic variables. Hirsute women had a Ferriman and Gallwey score ranging from 8 to 19. Psychometric evaluation for quality of life was carried out by the following methods: (a) Kellner's Brief Problem List, a 12 item self-rating list of psychosocial problems; (b) Kellner's Symptom Rating Test (SRT), a 46 item self-rating scale that yields a total score of distress as well as six subscales (anxiety, depression, somatic symptoms, anger-hostility, cognitive and psychotic symptoms); and (c) Marks' Social Situations Questionnaire (SSQ), a 30 item self-rating scale concerned with social phobia. Patients with hirsutism displayed significantly higher social fears at the SSQ than controls (P < 0.01). They also showed more anxiety (P < 0.01) and psychotic symptoms (P < 0.01) at the SRT, whereas there were no significant differences in depression, somatization, anger-hostility and cognitive symptoms. These results suggest that the complex management of hirsute women, in addition to pharmacological and/or cosmetic measures, may require specific psychotherapy.

Course of depression in Cushing's syndrome: response to treatment and comparison with Graves' disease.

Depression in a common, life-threatening complication of Cushing's syndrome and may occur in several other endocrine disorders. It is not clear, however, whether distinct features pertain to hypercortisolism. We studied depression in Cushing's syndrome differentiating pituitary-dependent and pituitary-independent forms, its incidence compared to Graves' disease, and its appearance in the prodromal phase of both conditions. To 66 consecutive patients with Cushing's syndrome and 70 with Graves' disease, after treatment, a semistructured interview for depressive symptoms based on Paykel's clinical interview for depression was administered. In Cushing's syndrome, the response of depression to normalization of urinary cortisol levels was evaluated by Kellner's global rating method. There was a significant difference in the occurrence of depression (p < 0.001) between Cushing's syndrome (62%) and Graves' disease (23%). Depression appeared in the prodromal phase in 27% of patients with Cushing's syndrome and in 14% of those with Graves' disease, but the difference was not significant. In Cushing's syndrome, there were no significant differences in depression between patients with pituitary-dependent (n = 41) and pituitary-independent (n = 20) forms, or in their response to treatment. About 70% of patients fully recovered from their depression, whereas there was no substantial change in the others and even worsening in 2. Our findings in Cushing's syndrome and Graves' disease are in agreement with previous investigations using specific diagnostic criteria for depression. We found a tendency for this symptom to manifest in the prodromal phase of both illnesses. An endocrine etiology should be, therefore, considered in depressed patients not responding to standard psychiatric treatment.