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Biomedical subjects

J Calabrese

Publications and source records attributed to J Calabrese.

At least 19 recordsLinked to original sources
PubMed2001

Case report: off-pump total myocardial revascularization for dextrocardia and situs inversus.

A 42-year-old man with dextrocardia and situs inversus underwent successful off-pump total myocardial revascularization using the technique popularized by Tector [Tector 1994, Tector 1996]. The free left internal mammary artery (LIMA) was anastomosed to the in-situ right internal mammary artery (RIMA) at the level of the right-sided left atrial appendage, then anastomosed sequentially to the first diagonal branch (D1) of the left anterior descending artery (LAD), and to the LAD. The in-situ RIMA was sequentially anastomosed to the first and the second obtuse marginal branches (OM1 and OM2) of the circumflex coronary artery. A saphenous vein was then anastomosed to a diffusely diseased posterior descending branch (PDA) of the right coronary artery (RCA). The patient was asymptomatic and in excellent condition three months after surgery. In economically depressed regions of the world, such as the Gaza Strip, off-pump complete revascularization is an excellent alternative to cardiopulmonary bypass.

Adult↗
PubMed1997

Effects of subchronic treatment with valproate on L-5-HTP-induced cortisol responses in mania: evidence for increased central serotonergic neurotransmission.

The mechanisms underlying the acute and prophylactic antimanic properties of valproate have remained elusive. There are some reports that treatment with valproic acid may increase brain serotonergic neurotransmission in the rodent. This study was carried out in order to investigate the effects of subchronic therapy with valproate on central serotonin metabolism in manic patients. Toward this end, the authors examined plasma cortisol responses to 200 mg (orally) L-5-hydroxy-tryptophan (L-5-HTP) in 10 manic patients both before and after subchronic treatment with valproate. Administration of L-5-HTP resulted in significantly increased cortisol responses both before and after treatment with valproate. The L-5-HTP-induced cortisol responses were significantly higher after treatment with valproate than before treatment. It is suggested that valproate may increase central serotonergic neurotransmission and that this stimulation may play a role in the antimanic effects of valproate.

5-Hydroxytryptophan↗
PubMed1997

Design, synthesis, and evaluation of tetrahydropyrimidinones as an example of a general approach to nonpeptide HIV protease inhibitors.

Re-examination of the design of the cyclic urea class of HIV protease (HIVPR) inhibitors suggests a general approach to designing novel nonpeptide cyclic HIVPR inhibitors. This process involves the inversion of the stereochemical centers of the core transition-state isostere of the linear HIVPR inhibitors and cyclization of the resulting core using an appropriate cyclizing reagent. As an example, this process is applied to the diamino alcohol class of HIVPR inhibitors to give tetrahydropyrimidinones. Conformational analysis of the tetrahydropyrimidinones and modeling of its interaction with the active site of HIVPR suggested modifications which led to very potent inhibitors of HIVPR (24 with a Ki = 0.018 nM). The X-ray crystallographic structure of the complex of 24 with HIVPR confirms the analysis and modeling predictions. The example reported in this study and other examples that are cited indicate that this process may be generally applicable to other linear inhibitors.

Binding Sites↗
PubMed1997

Effect size of efficacy measures comparing divalproex, lithium and placebo in acute mania.

Effect size (ES) is a statistical concept that can be used to improve the interpretation of results from psychopharmacological studies. ES may aid interpretation of results when sample size is unbalanced or small or when units or levels of baseline measures differ across items. Usually, an investigator can define a threshold value for a clinically meaningful ES based on published data and clinical judgment or by resorting to conventions, e.g., a medium ES = 0.5 S.D., which can usually be discerned by the trained clinician. In the present study, we apply ES analysis to results from a study comparing the effectiveness of divalproex (DIVAL), lithium (LI), and placebo (PLA) in hospitalized, acutely manic patients. One hundred seventy-six patients were randomly assigned to DIVAL, LI, or PLA in a 2:1:2 ratio, with drug administered in a double-blind, parallel group design for 21 days. The primary efficacy measure was the Mania Rating Scale from the Schedule for Affective Disorders and Schizophrenia, composed of the Manic Syndrome Score (MSS) from items that are relatively specific to the manic state, and the Behavior and Ideation Score (BIS), which reflects severe but nonspecific psychopathology. Improvement of the MSS after 5 days of treatment was difficult to interpret based on percentage change (DIVAL = 19%, LI = 13.5%, PLA = 8.5%). However, the corresponding effect sizes of 0.79, 0.55, and 0.35 indicated a medium to marked ES for DIVAL, a medium ES for LI, and a small ES for PLA at this early point in treatment. Similarly, the ES for change on the MSS at the end of treatment indicated a large, readily observable improvement with both DIVAL (ES = 1.01) and LI (ES = 0.79) vs. an ES of 0.37 for PLA. ES analysis also indicated that the BIS is a less robust indicator of change to either drug. The ES at the end of treatment for the BIS was 0.67 for DIVAL-, 0.62 for LI-, and 0.25 for PLA-treated patients.

Adolescent↗
PubMed1995

Alterations in plasma prolyl endopeptidase activity in depression, mania, and schizophrenia: effects of antidepressants, mood stabilizers, and antipsychotic drugs.

The activity of prolyl endopeptidase (PEP), a serine proteinase, has been found to be significantly lower in the blood of patients with major depression than in normal volunteers. The present study investigates plasma PEP activity in 25 major depressed, 10 manic, and 14 schizophrenic subjects versus 30 normal volunteers. It also examines the effects of antidepressants, valproate, and neuroleptic drugs on plasma PEP activity. PEP activity was significantly lower in major depressed subjects than in normal volunteers and in patients with mania and schizophrenia. In depressed subjects, plasma PEP activity was significantly increased during treatment with antidepressant drugs, such as fluoxetine. Plasma PEP activity was significantly increased in manic and schizophrenic subjects compared with normal volunteers. In manic subjects, short-term treatment with valproate had a significant suppressive effect on PEP activity. No significant effects of neuroleptics on PEP activity could be found in the schizophrenic patients. The results support the hypothesis that lower PEP activity could play a role in the pathophysiology of major depression, while increased PEP activity may be related to psychotic conditions, such as mania and schizophrenia.

Affect↗
PubMed1994

The relevance of the in- versus outpatient status for studies on HPA-axis in depression: spontaneous hypercortisolism is a feature of major depressed inpatients and not of major depression per se.

Increased spontaneous activity of the hypothalamic-pituitary-adrenal (HPA)-axis is frequently reported in major depressed inpatients. The aim of the present study was to determine whether there are differences in spontaneous HPA-axis activity between major depressed inpatients and outpatients. Toward this end, the authors measured basal 9:00 a.m. plasma cortisol and the integrated assessment of plasma morning cortisol secretion over 2 (AUC 120) hours in 48 major depressed inpatients, 17 major depressed outpatients and 73 normal volunteers. Major depressed inpatients exhibit significantly higher plasma cortisol values than healthy controls and major depressed outpatients. The cortisol data from the latter are not significantly different from these of the healthy controls. The cortisol differences between in and outpatients were still present after considering the influences of age, sex, body mass index, severity or endogeneity of illness, unipolar/bipolar subclassification, or specific symptoms such as suicidal thoughts, insomnia, psychomotor disorders, psychoticism, weight loss or anxiety. The results indicate that hypercortisolism as measured by basal morning plasma levels is not a feature of major depression per se, but rather of an interaction between the illness and hospitalization.

Adolescent↗
PubMed1994

Natural killer cell activity in major depression: relation to circulating natural killer cells, cellular indices of the immune response, and depressive phenomenology.

1. Recently, blunted natural killer cell activity (NKCA) has been found in major depression. The present study investigates the relationships between ex vivo blunted NKCA in major depression, number or percentage of NKC, in vivo indices of systemic immune activation and depressive phenomenology. 2. Toward this end, NKCA, absolute number of leukocytes and number or percentage of lymphocytes, monocytes, neutrophils, activated T lymphocytes (HLA-DR+, CD25+) and NKC (CD3-CD56+) were determined in 13 normal controls and 36 depressed inpatients. 3. NKCA was significantly and positively related to number and percentage of NKC in the peripheral blood. The major depression-related reduction in NKCA was not related to alterations in peripheral NKC. There were significant negative correlations between NKCA and number or percentage of leukocytes, monocytes, neutrophils and HLA-DR+ T cells. Up to 50% of the variance in NKCA could be explained by the regression on the number of monocytes, percentage of HLA-DR+ T and NKC cells, and diagnostic classification. Up to 43% of the variance in NKCA was explained by depressed mood, somatic anxiety and less diurnal variation. 4. The results show that blunted NKCA in major depression is not related to alterations in peripheral NKC, but reflects in part the systemic immune activation in that illness.

Adult↗
PubMed1994

Adrenocorticotropic hormone, beta-endorphin and cortisol responses to oCRH in unipolar depressed patients pretreated with dexamethasone.

1. Corticotropin-releasing hormone (ovine CRH, 100 micrograms intravenous bolus) was given to 63 unipolar depressed inpatients following the 1 mg overnight dexamethasone suppression test (DST). The depressed patients included 18 minor, 24 simple major and 21 melancholic subtypes. 2. Baseline or postdexamethasone plasma levels of intact adrenocorticotropic hormone (ACTH), beta-endorphin/beta-lipotropin (beta END/beta LPH), cortisol, and dexamethasone were measured, as well as the post DST+CRH hormone responses. 3. CRH administration 9.5 hr after dexamethasone resulted in a significant enhancement of ACTH, beta END/beta LPH and cortisol secretion. The post DST+CRH ACTH and beta END/beta LPH- but not cortisol-values exceeded their baseline hormone levels. The post DST+CRH ACTH--but not beta END/beta LPH or cortisol-levels were significantly higher in major depressives compared to minor depressives. The post DST+CRH ACTH and beta END/beta LPH--but not cortisol-levels were significantly higher in DST nonsuppressors than suppressors. The post DST+CRH ACTH levels were significantly and positively related to severity of illness. 4. The results provide evidence that the pathophysiology underlying the abnormal DST+CRH and DST tests in melancholia is localized at the pituitary level and may consist of a CRH-driven breakthrough of corticotropic cell secretion synergized by central and peripheral agents, in conjunction with a decrease in glucocorticoid feedback suppressibility.

Adrenocorticotropic Hormone↗
PubMed1994

Effects of age on spontaneous cortisolaemia of normal volunteers and depressed patients.

The aim of this study was to characterize the relationships between age and endogenous cortisol secretion in healthy controls and in major depressed patients between 18 and 58 years of age. Toward this end, the authors measured morning basal plasma cortisol secretion every 30 min from 0900 h until 1100 h and computed the integrated morning cortisol secretion in 80 normal controls and 118 major depressed patients. A significant negative correlation between age and plasma morning cortisol was found in normal volunteers but not in major depressives. The observed decrease in cortisol secretion with age in normal controls older than 35 years does not occur in major depressives. The middle age (+/- 35 years) appears to be an important turning point in hypothalamo-pituitary-adrenal (HPA)-axis function of normal persons vs. major depressives.

Adolescent↗
PubMed1994

Ultrasensitive assay for measuring the intact (1-39) ACTH molecule: an asset in depression research.

This study investigates the utility for depression research of an assay for intact (1-39) adrenocorticotropic hormone (ACTH) versus that of a previously employed (i.e., 1-17, 1-24 sequences) ACTH assay. ACTH plasma levels were measured using two different ACTH assays (labeled as intact versus nonintact) in 10 minor and 27 major depressed subjects undergoing the combined dexamethasone suppression (DST) and corticotropin-releasing hormone (CRH) test. Intact--but not nonintact--ACTH values were significantly correlated with the severity of illness. Major depressed subjects exhibited significantly higher post-DST+CRH intact ACTH values than minor depressives, whereas nonintact ACTH values were not significantly different between these groups. Post-DST+CRH intact ACTH values were significantly more closely related to post-DST+CRH cortisol than nonintact ACTH values. It is concluded that the assay of the intact ACTH molecule is an asset in depression research and should replace the previous less specific and sensitive ACTH assays.

Adrenocorticotropic Hormone↗
PubMed1994

Multisite data reanalysis of the validity of rapid cycling as a course modifier for bipolar disorder in DSM-IV.

OBJECTIVE: The validity of rapid cycling as a distinct course modifier for bipolar disorder was assessed by comparing patients with and without a history of rapid cycling (4 or more affective episodes in 12 months) on demographic, clinical, family history, and outcome variables. These data were also used to formulate operational criteria for the modifier. METHOD: Data on subjects with rapid-cycling (N = 120) and nonrapid-cycling (N = 119) bipolar disorder from four sites were pooled and analyzed by using case-control and historical cohort methods. RESULTS: The rapid-cycling group contained more women and more subjects from higher social classes than the nonrapid-cycling group. Family history did not differ between the groups. The diagnosis had predictive validity in that the rapid-cycling patients had more episodes than the nonrapid-cycling patients during prospective follow-up. The relationship between gender and episode frequency supported the validity of the cutoff point of 4-8 episodes per year. The data regarding whether patients with rapid cycling based on truncated episodes more closely resembled rapid-cycling or nonrapid-cycling patients were equivocal. Patients whose only rapid cycling was associated with antidepressants resembled spontaneously rapid-cycling patients, while the majority of spontaneously rapid-cycling patients also had periods of antidepressant-associated rapid cycling. CONCLUSIONS: The validity of rapid cycling as a distinct course modifier for bipolar disorder is supported by differences in gender, prospectively assessed outcome, and perhaps social class between rapid-cycling and nonrapid-cycling patients. The relationship of gender to episode frequency supports the cutoff of 4 or more episodes per year.

Adult↗
PubMed1993

Sleep disorders and anxiety as symptom profiles of sympathoadrenal system hyperactivity in major depression.

Recently, it has been reported that major depression is accompanied by an increased sympathoadrenal system (SAS) activity. In order to study the psychopathological correlates of SAS activity in depression, the authors measured the 24 h urinary excretion of catecholamines (CA), i.e., noradrenaline (NE), adrenaline (E), dopamine (DA) and the NE/E metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) in 80 unipolar depressed subjects. The excretion of these indices of SAS activity have been studied in relation to the depressive items of the Structured Clinical Interview for DSM-III (SCID) and the Hamilton Depression Rating Scale (HDRS). There were significant positive correlations between the SCID item sleep disorders and the HDRS item middle insomnia, on the one hand, and NE, E and DA excretion, on the other. The MHPG excretion in 24 h urine was significantly and negatively related to somatic anxiety and hypochondriasis. It is suggested that these intertwined relationships between increased CA turnover, sleep discontinuity and anxiety may reflect the occurrence of a hyperarousal state in some major depressives that may be regarded as a coping response to various putative noxious stimuli.

Adrenal Glands↗
PubMed1993

Relationships between interleukin-6 activity, acute phase proteins, and function of the hypothalamic-pituitary-adrenal axis in severe depression.

Recent studies from this laboratory have provided some evidence that major depression, in particular melancholia, may be accompanied by an immune response. The present study was designed to investigate whether severe depression is characterized by increased interleukin-6 (Il-6) activity and whether Il-6 production is related to altered levels of acute phase reactants and to abnormal function of the hypothalamic-pituitary-adrenal (HPA) axis. Measurements were made in 8 healthy control subjects and 24 depressed inpatients of Il-6 production in culture supernatants of mitogen-stimulated peripheral leukocytes and plasma levels of haptoglobin (Hp), transferrin (Tf), and postdexamethasone cortisol. Il-6 activity was significantly higher in melancholic subjects than in healthy control subjects and in patients with minor depression or nonmelancholic major depression. Il-6 production was significantly correlated with Hp (positively) and Tf (negatively) plasma levels. There were significant and positive correlations between Il-6 activity and postdexamethasone cortisol values. The findings may suggest that increased Il-6 activity in severe depression is related to hypotransferrinemia, hyperhaptoglobinemia, and hyperactivity of the HPA axis.

Acute-Phase Proteins↗
PubMed1993

Psychomotor retardation, anorexia, weight loss, sleep disturbances, and loss of energy: psychopathological correlates of hyperhaptoglobinemia during major depression.

Recently, we have established that major depression is characterized by hyperhaptoglobinemia, which may be regarded as an index of an "acute" phase response in that illness. The present study investigates the psychopathological correlates of increased plasma concentrations of haptoglobin (Hp) in major depression. To this end, the authors studied the Hp levels in relation to depressive items of the Structured Clinical Interview for DSM-III (SCID) and the Hamilton Rating Scale for Depression (HRSD) in 90 depressed subjects. There was a significant positive relationship between the SCID symptoms anorexia/weight loss, sleep, and psychomotor disorders and Hp plasma concentrations. Hp plasma levels were significantly and positively correlated with overall severity of illness (HRSD). The HRSD symptom correlates of higher Hp levels were loss of interest, middle insomnia, and psychomotor retardation. Up to 31.4% of the variance in Hp plasma values could be explained by psychomotor disorders, anorexia, weight loss, middle insomnia, and less diurnal variation of mood. It is suggested that hyperhaptoglobinemia, as an index of an "acute" phase response in major depression, is related to the somatic dimension of depressive illness.

Acute-Phase Reaction↗
PubMed1993

Relationships between lower plasma L-tryptophan levels and immune-inflammatory variables in depression.

Despite much research, the pathophysiology underlying lower L-tryptophan (L-TRP) availability in major depression has remained elusive. The present study investigates whether lower L-TRP availability in major depression is related to immune activation which may occur in that illness and is known to modulate L-TRP metabolism. Toward this end, the authors have measured the following in depressed patients and normal control subjects: plasma levels of L-TRP, and the competing amino acids (CAA) valine, leucine, isoleucine, tyrosine, and phenylalanine, together with indices of immune function such as haptoglobin (Hp) and transferrin (Tf) plasma levels, dipeptidyl peptidase IV (DPP IV) serum activity, and mitogen-induced culture supernatant interleukin-6 (Il-6) production. Both plasma levels of L-TRP and the L-TRP/CAA ratio were significantly lower in major depressed subjects as compared with healthy control subjects. There were significant correlations between plasma L-TRP levels, on the one hand, and Tf plasma levels, DPP IV activity (both positive), Il-6 production, and Hp plasma levels (both negative), on the other. Up to 63.7% of the variance in L-TRP plasma concentrations could be explained by DPP IV, Hp, Il-6 values, and gender. Up to 50% of the variance in the L-TRP/CAA ratio could be explained by Hp values (negative correlation) and gender. It is hypothesized that lower plasma L-TRP availability in major depression may be related to the immune response in that illness.

Adult↗
PubMed1993

Regional cerebral blood flow in unipolar depression measured with Tc-99m-HMPAO single photon emission computed tomography: negative findings.

Recent studies have reported that patients with unipolar major depression may show a lower whole brain cerebral blood flow (CBF) and reduced regional CBF in frontal, temporal, and parietal lobes. The present study used single photon emission computed tomography (SPECT) with the CBF marker Tc-99m-hexamethylpropyleneamineoxine (HMPAO) to measure the cortical CBF of six individual regions of interest (ROIs), total ROI, and left or right hemispheric total ROI in 43 unipolar depressed subjects and 12 normal control subjects. There were no significant differences in the distribution of Tc-99m-HMPAO uptake into total ROI, right or left global ROI, prefrontal, motor frontal, parietal, temporal, visual cortex, or associative visual cortex between patients with melancholic depression, simple major depression, or minor depression and healthy control subjects. There were also no significant differences in the right-left distribution of uptake between the patients and the control subjects. Hypoperfusion was observed in motor frontal and parietal cortex of patients who had been taking benzodiazepines during the study period. It is concluded that cortical CBF, as assessed with Tc-99m-HMPAO SPECT, is relatively intact in the present sample of patients with severe depression.

Adult↗
PubMed1993

Autoimmunity in depression: increased antiphospholipid autoantibodies.

Some groups have recently reported higher titers of autoantibodies in depressed subjects than in normal controls. The present study investigates whether depressed patients exhibit increased antiphospholipid antibody titers compared with normal controls. The authors measured the binding index (BI) of antiphosphatidylserine (APSA), antipartial thromboplastin (APTA) and anticardiolipin (ACA) in 22 minor, 23 simple major and 20 melancholic depressives, 10 healthy controls and 104 normal controls with negative autoantibody sera. Depressed subjects exhibited significantly higher APSA and APTA antibody titers compared with normal controls. A large number of depressed subjects (+/- 54%) showed APTA and APSA positivity, defined as BI > or = 2 standard deviations above the mean BI of normal controls. There was a significant discrimination (> or = 2.8 standard deviations) between melancholic subjects and healthy controls with respect to BI of ACA, APSA and APTA. However, by using a more conservative value for phospholipid positivity (i.e., BI > or = 5 standard deviations above the mean BI of a reference sample of normal sera), the subject's autoantibody titers were, on the whole, within the normal range. Our results point towards a higher expression of antiphospholipid antibodies during depression but a much lower incidence of positive patients than in classical autoimmune disorders, such as systemic lupus erythematosus.

Adult↗