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Biomedical subjects

A Cappiello

Publications and source records attributed to A Cappiello.

At least 19 recordsLinked to original sources
PubMed2001

Micro-SPE method for sample introduction in capillary HPLC/MS.

A new solid-phase extraction on-line device for micro-HPLC is presented. This device optimizes the injection of very dilute samples into a packed capillary column. It consists of two capillary, reversed-phase, HPLC columns of different length that can be linked together as a single chromatographic column. The first segment, only 2 cm long is connected to the HPLC injector. When disconnected from the longer column, several milliliters of an aqueous sample can be passed through at a high flow rate for fast trapping. On the basis of the retention mechanism, all suitable compounds are focused on the short column head in a sharp band. As soon as the chromatographic column is recomposed, the trapped analytes are eluted and separated at the optimal flow rate and gradient conditions. Due to the high preconcentration factor, trace-level analysis can be performed successfully. Different classes of analytes of various polarities and molecular weights can be determined, depending on the stationary phase and on the detector used. Some pesticides belonging to different classes were chosen to evaluate the performance of the device using an electron ionization mass spectrometer as HPLC detector. A fungicide in an irrigation canal water was determined at a concentration level of 4.5 microg x L(-1).

Journal Article↗
PubMed2000

An efficient liquid chromatography--mass spectrometry interface for the generation of electron ionization spectra

The use of a new LC-MS interface (cap-EI), part of a Waters Integrity system, capable of generating EI spectra at micro flow rates is presented. The cap-EI interface relies on the production of a fine aerosol by means of a nebulizer and supported by a nitrogen jet. Sensitivity, response linearity, reproducibility, and LC compatibility of the interface were thoroughly examined using testosterone, caffeine, a mixture of antiinflammatory drugs, and 3,4-dihydroxybenzoic acid as test compounds. The interface is fully compatible with LC requirements such as high-water- and/or -buffer-content mobile phases. Reproducibility, high sensitivity in scan mode, as well, to produce library-searchable EI spectra, 2 orders of magnitude linearity, together with an intrinsic simplicity of the entire system are the key features of cap-EI interface.

Journal Article↗
PubMed2000

Antidepressant effects of ketamine in depressed patients.

BACKGROUND: A growing body of preclinical research suggests that brain glutamate systems may be involved in the pathophysiology of major depression and the mechanism of action of antidepressants. This is the first placebo-controlled, double-blinded trial to assess the treatment effects of a single dose of an N-methyl-D-aspartate (NMDA) receptor antagonist in patients with depression. METHODS: Seven subjects with major depression completed 2 test days that involved intravenous treatment with ketamine hydrochloride (.5 mg/kg) or saline solutions under randomized, double-blind conditions. RESULTS: Subjects with depression evidenced significant improvement in depressive symptoms within 72 hours after ketamine but not placebo infusion (i.e., mean 25-item Hamilton Depression Rating Scale scores decreased by 14 +/- SD 10 points vs. 0 +/- 12 points, respectively during active and sham treatment). CONCLUSIONS: These results suggest a potential role for NMDA receptor-modulating drugs in the treatment of depression.

Adult↗
PubMed2000

SPECT [I-123]iomazenil measurement of the benzodiazepine receptor in panic disorder.

BACKGROUND: Alterations in benzodiazepine receptor function have long been hypothesized to play a role in anxiety. Animal models of anxiety involving exposure to chronic stress have shown a specific decrease in benzodiazepine receptor binding in frontal cortex and hippocampus. The purpose of this study was to examine benzodiazepine receptor binding patients with panic disorder and comparison subjects. METHODS: A quantitative measure related to benzodiazepine receptor binding (Distribution Volume (DV)) was obtained with single photon emission computed tomography (SPECT) imaging of [123I]iomazenil and measurement of radioligand concentration in plasma in patients with panic disorder and healthy controls. DV image data were analyzed using statistical parametric mapping (spm96). RESULTS: A decrease in measures of benzodiazepine receptor binding (DV) was found in left hippocampus and precuneus in panic disorder patients relative to controls. Panic disorder patients who had a panic attack compared to patients who did not have a panic attack at the time of the scan had a decrease in benzodiazepine receptor binding in prefrontal cortex. CONCLUSIONS: Findings of a decrease in left hippocampal and precuneus benzodiazepine receptor binding may be related to alterations in benzodiazepine receptor binding, or other factors including changes in GABAergic transmission or possible endogenous benzodiazepine compounds. Benzodiazepine receptor function in prefrontal cortex appears to be involved in changes in state-related panic anxiety.

Adolescent↗
PubMed2000

Attenuation of the neuropsychiatric effects of ketamine with lamotrigine: support for hyperglutamatergic effects of N-methyl-D-aspartate receptor antagonists.

BACKGROUND: The cognitive, behavioral, and mood effects of N-methyl-D-aspartate (NMDA) receptor antagonists, such as phencyclidine and ketamine, have been used to study the effects of NMDA receptor dysfunction. Pharmacological modulation of the effects of NMDA receptor antagonists, such as ketamine, may lead to development of novel therapeutic agents for psychiatric illnesses such as schizophrenia. Preclinical studies indicate that some ketamine effects may be mediated through increased glutamate release. In this study, we tested the hypothesis that lamotrigine, a drug reported to inhibit glutamate release, will reduce the neuropsychiatric effects of ketamine in humans. METHOD: Healthy subjects (n = 16) completed 4 test days involving the administration of lamotrigine, 300 mg by mouth, or placebo 2 hours prior to administration of ketamine (0.26 mg/kg by intravenous bolus and 0.65 mg/kg per hour by intravenous infusion) or placebo in a randomized order under double-blind conditions. Behavioral and cognitive assessments were performed at baseline and after administration of the medications. RESULTS: Lamotrigine significantly decreased ketamine-induced perceptual abnormalities as assessed by the Clinician-Administered Dissociative States Scale (P<.001); positive symptoms of schizophrenia as assessed by the Brief Psychiatric Rating Scale positive symptoms subscale (P<.001); negative symptoms as assessed by the Brief Psychiatric Rating Scale negative symptoms subscale (P<.05); and learning and memory impairment as assessed by the Hopkins Verbal Learning Test (P<.05). However, lamotrigine increased the immediate mood-elevating effects of ketamine (P<.05). CONCLUSIONS: Glutamate release-inhibiting drugs may reduce the hyperglutamatergic consequences of NMDA receptor dysfunction implicated in the pathophysiologic processes of neuropsychiatric illnesses such as schizophrenia. Further study is needed.

Adult↗
PubMed2000

Factors influencing survival after resection for ductal adenocarcinoma of the head of the pancreas.

BACKGROUND AND OBJECTIVES: Recent reports have demonstrated improvement in the 5-year actuarial survival for patients with resected ductal adenocarcinoma. The purpose of this study is to determine the factors favoring long-term survival after pancreaticoduodenectomy. METHODS: Between 1974 and 1995, 75 patients with pancreatic head carcinoma underwent pancreaticoduodenectomy in our department. RESULTS: Overall postoperative mortality rate was 5. 3% and morbidity was 24%. Median survival following resection was 17 months. Estimated 1-, 2-, and 5-year survival rates were 68%, 46.7%, and 18.7%, respectively. Five-year survival was greater for node-negative than for node-positive patients (41.7% vs. 7.8%, P < 0. 001) and for smaller (<3 cm) than for larger tumors (33.3% vs. 8.8%, P < 0.006). The 5-year survival in patients with negative margins (n = 60) was 23.3%, whereas no patient with positive margins (n = 15) survived at 13 months (P < 0.001). Multivariate analysis, performed by the Cox proportional hazards model, indicated that margin status, lymph node metastasis, tumor size, and poor histological differentiation were independent predictors of poor survival. CONCLUSIONS: Five-year survival for patients undergoing pancreaticoduodenectomy for ductal adenocarcinoma of the pancreas was 18.7%. Survival was greater in the group of patients with negative lymph nodes, tumor size <3 cm, and negative margin status.

Actuarial Analysis↗
PubMed1999

Liquid chromatographic-mass spectrometric determination of phenolic compounds using a capillary-scale particle beam interface.

A capillary-scale particle beam interface was used to detect 18 phenolic compounds in red wine samples. This technique allows reproducible, library searchable electron ionization spectra at only 1 microliter/min mobile phase flow-rate for a sensitive detection of the analytes in complex matrices. The method makes use of a narrow bore, reversed-phase packed capillary column for sample separation. Detection limits were in the low picogram range for most compounds. Sensitivity and response linearity were evaluated for eight phenolic acids, which are often encountered in red wines. The phenolic compound composition was outlined in two red wines obtained using different aging processes.

Chromatography, Liquid↗
PubMed1999

The use of pindolol with fluoxetine in the treatment of major depression: final results from a double-blind, placebo-controlled trial.

BACKGROUND: Preliminary reports have suggested that concomitant institution of pindolol and serotonin reuptake inhibitors robustly hastens clinical response; however, contradictory evidence from a randomized double-blind, controlled trial was recently reported by this group in a population of depressed patients who were prescribed fluoxetine and pindolol. Herein, we report final results from an extended sample size. METHODS: Drug-free outpatients with a major depressive episode were randomized in a double-blind manner to one of two treatment conditions: fluoxetine (20 mg daily) with pindolol (7.5 to 10 mg daily) or fluoxetine (20 mg daily) with placebo. After 6 weeks, patients were followed for 3 more weeks in a single-blind manner, on fluoxetine and placebo pindolol. RESULTS: Eighty-six patients completed at least 1 or more weeks on protocol, with 45 and 41 patients randomized to the pindolol and placebo groups respectively. After 2 weeks on protocol, partial remission (i.e., at least 50% decrease in depression rating scores from baseline) rates for pindolol (16%) and placebo (19%) groups were comparable. By the study's end, a partial remission was achieved, at least transiently, for 67% of the pindolol group and 80% of the placebo group. Pindolol treatment was associated with statistically significant reduction in blood pressure and pulse as compared to the control group. The two groups did not have overall differences in rates of attrition, time to response, and side effects. CONCLUSIONS: In accord with our previously published findings, these extended results do not support the efficacy of pindolol in hastening clinical response to fluoxetine in a patient population with predominantly chronic and recurrent depression.

Adult↗
PubMed1999

Effect of catecholamine depletion on lithium-induced long-term remission of bipolar disorder.

BACKGROUND: This study investigated the effects of catecholamine depletion with alpha-methylparatyrosine (AMPT) on mood indices in patients with bipolar disorder who were in long-term remission with lithium therapy. METHODS: Eight subjects with DSM-IV bipolar disorder currently in remission for > 3 months on lithium were included in the study. Subjects were given either AMPT or placebo, in a randomized double-blind manner, in two test sessions of 4 days each. RESULTS: Subjects did not have any significant changes in mood during AMPT or placebo administration; however, 24-48 hours after the last active AMPT dose subjects had a transient relapse of hypomanic symptoms. Relapse of hypomanic symptoms did not correlate with increases in serum levels of homovanillic acid or 3-methoxy-4-hydroxyphenylglycol. CONCLUSIONS: These findings suggest that the mechanism of prevention of manic relapse by long-term lithium therapy may be dependent on stability of the catecholamine system.

Adult↗
PubMed1999

Transient depressive relapse induced by catecholamine depletion: potential phenotypic vulnerability marker?

BACKGROUND: Although state-related alterations in catecholamine function have been well-described in depressed subjects, enduring abnormalities have been less reliably identified. In our study, medication-free subjects with fully remitted major depression underwent a paradigm of catecholamine depletion, via use of the tyrosine hydroxylase inhibitor alpha-methylparatyrosine. METHOD: Subjects underwent 2 sets of testing conditions in a double-blind, random-ordered, crossover design, approximately 1 week apart. They underwent active catecholamine depletion (via oral administration of 5 g alpha-methylparatyrosine) or sedation-controlled, sham catecholamine depletion (via oral administration of 250 mg diphenhydramine hydrochloride), during a 2-day observation. Serial mood ratings and blood samples were obtained. RESULTS: Fourteen subjects completed the active testing condition; 13 completed sham testing. Subjects experienced marked, transient increases in core depressive and anxiety symptoms, as demonstrated by a mean 21-point increase on Hamilton Depression Rating Scale scores. Furthermore, 10 (71%) of 14 subjects fulfilled relapse criteria during active testing, whereas 1 (8%) of 13 subjects did so during sham testing. The severity of the depressive reaction correlated with baseline plasma cortisol levels (r = 0.59; P =.04). CONCLUSIONS: Euthymic, medication-free subjects with a history of major depression demonstrate significant depressive symptoms when undergoing testing with alpha-methylparatyrosine. This depressive reaction may represent a reliable marker for a history of depression. Further work is needed to clarify the significance of this finding.

Adult↗
PubMed1998

Lithium and desipramine versus desipramine alone in the treatment of severe major depression: a preliminary study.

Improvement following lithium augmentation is well-documented in depressed patients resistant to tricyclic antidepressants. However, response latency to lithium augmentation is extremely variable, suggesting other mechanisms may be involved. To evaluate whether long-term tricyclic treatment is necessary for lithium augmentation's effect, the rapidity and magnitude of response to lithium combined with desipramine from the start of treatment was compared to desipramine alone in severely depressed patients. Patients with DSM-III-R major depression were randomized to double-blind, placebo-controlled treatment with either lithium + desipramine or placebo + desipramine for 4 weeks. Response criteria were based on Hamilton Depression Rating Scale scores and global improvement. Analysis of covariance of Hamilton scores demonstrated that lithium + desipramine was superior to placebo + desipramine at week 1 (P < 0.009), week 2 (P < 0.028), and week 3 (P < 0.07), although not at week 4. There were more responders to the combination than to monotherapy (P < 0.042). These preliminary data suggest that lithium + desipramine may have some efficacy in severely depressed patients. Further studies with larger samples are needed to confirm these findings.

Adult↗
PubMed1997

Use of nonvolatile buffers in liquid chromatography/mass spectrometry: advantages of capillary-scale particle beam interfacing.

The use of nonvolatile buffers like phosphate and citrate is usually incompatible with mass spectrometric detection or may heavily interfere with ion generation. In the case of conventional HPLC flow rates, the continuous buffer deposition produces fouling of the mass spectrometer ion source and may worsen the performance of any LC/MS interface as well. Our research group demonstrated that reducing the mobile phase flow rate in a particle beam interface improves the nebulization and enhances the overall performance. We have also assumed that such a modification may better handle potentially instrument harmful solvents or nonvolatile HPLC buffers. Since the presence of salts does not interfere with the electron ionization process, the particle beam interface can be considered, in principle, particularly suitable for those chromatographic separations that benefit from nonvolatile buffers. The microscale flow rate interface, developed in our laboratory, generates an aerosol from 1 microL/min of mobile phase flow rate. Under these conditions, the absolute amount of a nonvolatile buffer actually introduced into the system is approximately 1/1000 of that carried by a conventional HPLC column, slowing its deposition. This assumption was verified with a real-world application requiring the use of a phosphate buffer at a maximum concentration of 10 mM. It involved the determination of dexamethasone, an anti-inflammatory drug, in human blood after its administration to a patient. Several crucial mass spectral and chromatographic parameters were monitored during a 35-day period of intense use. Neither appreciable signal modification nor evident buffer deposition was observed during the test period, with only a normal and limited run-by-run and day-by-day variation of the instrument response.

Anti-Inflammatory Agents↗
PubMed1997

Surgical revascularization for acute coronary insufficiency: analysis of risk factors for hospital mortality.

BACKGROUND: A retrospective study of 444 patients undergoing urgent and emergent coronary artery bypass grafting for acute coronary insufficiency was performed to identify the risk factors for hospital death specifically associated with the clinical severity of the acute coronary insufficiency syndrome. METHODS: The patients were divided into three groups-urgent, emergent A, and emergent B-on the basis of the evolution of the clinical pattern of the acute coronary insufficiency syndrome on full medical treatment. The three categories were defined as follows: urgent (257 patients), surgical revascularization could be delayed for 24 to 36 hours after surgical consultation because of adequate control of ischemia; emergent A (127 patients), prompt myocardial revascularization was required because medical treatment achieved only transient regression of an unrelenting ischemic pattern; and emergent B (60 patients), prompt myocardial revascularization was required because the acute coronary insufficiency was entirely refractory to medical treatment. RESULTS: Mortality rates were 7.4% for the urgent group, 13.4% for the emergent A group, and 31.7% for the emergent B group. Multivariate analysis identified the following as risk factors for hospital mortality: ejection fraction (p = 0.023) and aortic cross-clamp time (p = 0.10) for the urgent group; aortic cross-clamp time (p = 0.017), ejection fraction (p = 0.03), and nonuse of blood cardioplegia (p = 0.04) for the emergent A group; and cardiogenic shock (p = 0.00), preoperative ischemic interval (p = 0.00), aortic cross-clamp time (p = 0.018), and nonuse of blood cardioplegia (p = 0.012) for the emergent B group. CONCLUSIONS: A more exact definition of patient risk can be achieved when predictive outcome models are constructed using the risk factors specifically related to each level of clinical severity of the ischemic syndrome.

Blood↗
PubMed1997

Effects of antiglucocorticoid treatment on 5-HT1A function in depressed patients and healthy subjects.

Clinical studies suggest that 5-HT1A receptor function may be blunted in depression, while 5-HT1A agonists may possess antidepressant activity. Preclinical findings implicate changes in 5-HT1A receptor sensitivity in the mechanism of antidepressant action. The hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis in depression could be related to those observations, since 5-HT1A receptors are inhibited by glucocorticoids. To evaluate the interaction of the HPA and 5-HT1A systems, we pretreated 15 unipolar depressed patients and 12 healthy control subjects with the antiglucocorticoid ketoconazole (KTCZ) prior to administration of a test dose of the 5-HT1A agonist ipsapirone (IPS). Neuroendocrine (ACTH, cortisol, growth hormone), physiological (hypothermia), and behavioral responses to IPS were assessed. As expected, KTCZ inhibited cortisol biosynthesis, but non-HPA responses to IPS were not enhanced. This study failed to show that glucocorticoid modulation of 5-HT1A receptor function is altered in depression.

Adrenocorticotropic Hormone↗
PubMed1996

Seasonal variation in neuroendocrine and mood responses to i.v. L-tryptophan in depressed patients and healthy subjects.

Seasonality of mood disorders might involve alterations in the rhythmicity of serotonin [5-HT] function. We examined seasonal effects on the neuroendocrine and mood responses to L-tryptophan (L-TRP) in depressed patients and healthy subjects. In this study, 126 drug-free patients with DSM-III-R major depression and 58 healthy subjects received in i.v. infusion of L-TRP. Serum prolactin (PRL) and plasma tryptophan levels were measured. Mood was assessed with visual analogue scales. Cosinor analysis revealed seasonal variation in peak change (delta) PRL and baseline tryptophan levels in the combined depressed and in unipolar, nonmelancholic, and nonpsychotic patients. Peak delta PRL and tryptophan levels were inversely correlated in combined depressed and unipolar patients. Seasonality was more evident in female than in male patients. These data support previous evidence that 5-HT function is abnormal in depression and further suggest a seasonal variability of such abnormalities that is absent in healthy subjects.

Adult↗
PubMed1995

[Surgical revascularization in acute coronary insufficiency: an analysis of the risk factors for hospital mortality in urgencies and emergencies].

OBJECTIVES: A retrospective analysis of 444 patients (Pts) with acute coronary insufficiency (A.C.I.) submitted to coronary artery bypass grafting between January '85 and December '92 was performed in order to identify incremental risk factors associated with perioperative mortality and to evaluate whether prediction of mortality can be accomplished utilizing risk models specifically linked to the severity of myocardial ischemia. METHODS: Based on clinical and ECGraphic standpoints three different groups were identified: urgent group, comprehensive of 257 Pts. in whom, because of full medically controlled ischemia, myocardial revascularization could be delayed until to 24-48 hours. Emergency-A group, comprehensive of 127 Pts with recurrent ischemia despite medical therapy, but with no signs of coronary insufficiency at the time of institution of cardiopulmonary bypass (CPB). Emergency-B group, comprehensive of 60 Pts operated on after a mean preoperative ischemic interval of 3.9 +/- 2.4 hours who presented unrelenting signs of ischemia, either persisting since the inception of the clinical picture or lasting for over 30 minutes at the time of institution of CPB; among those, 27 Pts were in cardiogenic shock. RESULTS: Mortality rate in the three groups was respectively: 7.4%, 13.4%, 31.7%. Multivariate analysis identified the following risk factors of in-hospital mortality: urgent group: aortic cross-clamping time (A.C.C.T.) (p = 0.10) and ejection fraction (E.F.) (p = 0.023). Emergency-A group: A.C.C.T. (p = 0.017), E.F. (p = 0.023) and non-use of blood cardioplegia (B.C.) (p = 0.04). Emergency-B group: cardiogenic shock (p = 0.00), preoperative ischemic interval > 6 hours (p = 0.00), A.C.C.T. (p = 0.018) and non-use of B.C. (p = 0.012). CONCLUSIONS: A useful stratification of Pts with A.C.I. in three different groups, each with its own risk model, can be obtained by means of clinical-ECGraphic criteria alone. Different prognostic weights can be attributed to the variables A.C.C.T., E.F. and non-use of B.C. depending on clinical status. A significant reduction of mortality rate in Pts with cardiogenic shock can be achieved by the utilization of individually-tailored surgical management.

Acute Disease↗