PubMed Health⌕ Search

Biomedical subjects

F Benedetti

Publications and source records attributed to F Benedetti.

At least 55 records · Page 3Linked to original sources
PubMed1999

Inducing placebo respiratory depressant responses in humans via opioid receptors.

Several lines of evidence indicate that placebos produce analgesia through the activation of endogenous opioid systems. Recently, we showed that placebos may also produce respiratory depressant responses, a typical side-effect of narcotics, when a subject had a prior experience of respiratory depression in the course of narcotic treatment. In the present study, we report that the placebo respiratory depression can be induced after repeated administrations of the partial opioid agonist buprenorphine. The placebo respiratory depressant effect that resulted from the buprenorphine conditioning was completely blocked by a dose of 10 mg of naloxone, indicating that it was mediated by endogenous opioids. These findings show that placebos act, via the activation of opioid receptors, not only on pain mechanisms but on the respiratory centres as well, thus mimicking a typical side-effect of narcotics. In addition, the experimental procedure we used did not produce any expectation of respiratory depression and, similarly, the subjects did not notice any sign of respiratory discomfort. Thus, the placebo respiratory depression elicited in the present study cannot be explained on the basis of cognitive or motivational mechanisms. Rather, it appears to be a sequence effect due to learning, thus suggesting a conditioning mechanism mediated by endogenous opioids.

Aged↗
PubMed1999

Ongoing lithium treatment prevents relapse after total sleep deprivation.

Forty bipolar depressed inpatients underwent three consecutive cycles of total sleep deprivation (TSD). At the beginning of the study, 20 patients were free of psychotropic drugs and 20 had been receiving lithium medication for at least 6 months. Mood was rated on the Hamilton Rating Scale for Depression before and after TSD; perceived mood changes during treatment were evaluated with self-administered visual analog scales. Patients undergoing long-term lithium treatment showed a significantly better response to TSD as rated on both scales: 13 of 20 patients (vs. 2 of 20 patients without lithium) showed a sustained response during a follow-up period of 3 months. This preliminary evidence of a positive interaction of TSD and long-term lithium treatment could be explained by a synergistic effect of both treatments on brain serotonergic function, possibly via a desensitization of 5-hydroxytryptamine-1A inhibitory autoreceptors.

Bipolar Disorder↗
PubMed1999

Influence of a functional polymorphism within the promoter of the serotonin transporter gene on the effects of total sleep deprivation in bipolar depression.

OBJECTIVE: A functional polymorphism in the transcriptional control region upstream of the coding sequence of the 5-hydroxytryptamine transporter (5-HTT) has been reported. This polymorphism has been shown to influence the antidepressant response to fluvoxamine and paroxetine. The authors tested the hypothesis that the allelic variation of the 5-HTT-linked polymorphic region (5-HTTLPR) could influence the response of depressed patients to total sleep deprivation. METHOD: Sixty-eight drug-free inpatients with bipolar depression underwent a night of total sleep deprivation. 5-HTTLPR was genotyped in these patients. Changes in perceived mood were rated on a visual analogue scale and analyzed by using repeated measures analysis of covariance. RESULTS: Patients who were homozygotic for the long variant of 5-HTTLPR showed a significantly better mood amelioration after total sleep deprivation than those who were heterozygotic and homozygotic for the short variant. CONCLUSIONS: The influence of 5-HTTLPR on response to total sleep deprivation is similar to its observed influence on response to serotonergic drug treatments. This finding supports the hypothesis of a major role for serotonin in the mechanism of action of total sleep deprivation in depression.

Adult↗
PubMed1998

The unipolar-bipolar dichotomy and the response to sleep deprivation.

Fifty-one inpatients affected by a major depressive episode were divided into four groups according to mood disorder diagnosis and previous clinical history (bipolar disorder type I; bipolar disorder type II; major depressive disorder with at least three previous depressive episodes; and single depressive episode patients) and administered three consecutive total sleep deprivation (TSD) cycles. Mood changes were rated with a reduced version of the Hamilton Depression Rating Scale and with self-administered visual analogue scales. TSD caused better clinical effects in bipolar and single-episode patients; in particular, unipolar patients lacked effects in perceived mood after the first TSD and showed worse Hamilton ratings in respect to the other groups after the three TSD treatments. Discriminant function analysis could correctly classify 80% of bipolar patients, post hoc, based on TSD response. Further researches on the clinical efficacy of TSD must take into account the heterogeneity of depression and of its biological substrate.

Adult↗
PubMed1998

A competitive immunoassay for the detection of esterolytic activity of antibodies and enzymes.

Screening of a large number of clones produced in a fusion is often the bottleneck in the isolation of catalytic antibodies. The usual approach requires two steps: clones are first selected for their high affinity to the antigen, and then the good binders are tested for their catalytic activity. To simplify this selection process, a competitive enzyme-linked immunosorbent assay (ELISA) has been developed that allows direct screening of the antibodies on the basis of their catalytic activity. In this assay, the product of the catalyzed reaction binds to an immobilized anti-product antibody in competition with a peroxidase-product conjugate. The screening assay has been developed for the antibody-catalyzed hydrolysis of esters of p-aminophenylacetic acid and has been tested on the porcine liver esterase (PLE)-catalyzed hydrolysis of the same substrates. This test allows the detection of product formation at the nanomolar level, while, in a typical assay, the catalytic activity of PLE can be traced down to 200 fmol of enzyme. Under standard conditions for the screening of hybridomas obtained from a fusion, the competitive ELISA allows detection of catalytic species with values of kcat > or = 5 x 10(-7) mol l-1 s-1 and kcat/kuncat > or = 50. While the assay has been designed for the selection of catalytic antibodies, other potential applications of this methodology are in the screening of libraries of engineered and designed enzymes and, in general, in the quantitative measurement of enzyme activity.

Animals↗
PubMed1998

Perceived mood and skin body temperature rhythm in depression.

Eighteen inpatients affected by recurrent major depression were monitored in their clinical and biological features during the acute episode of illness. Diurnal mood variations rated with Visual Analogue Scale (VAS) and diurnal variations of skin body temperature were measured every 2 h consecutively for 2 days. Circadian rhythmicity of the two parameters was evaluated by cosinor analysis separately for each patient. The inspection of the individual cosine fitting shows that patients with a high circadian rhythmicity in perceived severity of symptomatology tend to show low circadian rhythmicity in skin body temperature, whereas patients with a low VAS oscillation tend to display a higher diurnal variation in skin body temperature. A chi-square test confirmed a statistical significance of the discordance between the two rhythms. We discuss our findings hypothesizing a different degree of entrainment of the disease process to the main circadian pacemaker.

Adult↗
PubMed1998

Neurophysiologic assessment of nerve impairment in posterolateral and muscle-sparing thoracotomy.

OBJECTIVE: This study was aimed at analyzing the degree of intercostal nerve impairment in posterolateral and muscle-sparing thoracotomy and at correlating the nerve damage to the severity of long-lasting postthoracotomy pain. METHODS: Neurophysiologic recordings were performed 1 month after either posterolateral or muscle-sparing thoracotomy to assess the presence of the superficial abdominal reflexes (mediated in part by the intercostal nerves), the somatosensory-evoked responses after electrical stimulation of the surgical scar, and the electrical thresholds for tactile and pain sensations of the surgical incision. RESULTS: The patients who underwent a posterolateral thoracotomy showed a higher degree of intercostal nerve impairment than the muscle-sparing thoracotomy patients as revealed by the disappearance of the abdominal reflexes, a larger reduction in amplitude of the somatosensory-evoked potentials, and a larger increase of the sensory thresholds to electrical stimulation for both tactile perception and pain. In addition, these neurophysiologic parameters were highly correlated to the postthoracotomy pain experienced by the patients 1 month after surgery, indicating a causal role for nerve impairment in the long-lasting postoperative pain. CONCLUSIONS: This study shows for the first time the pathophysiologic differences between posterolateral and muscle-sparing thoracotomy and suggests that the minor long-lasting postthoracotomy pain in muscle-sparing thoracotomy patients is partly due to a minor nerve damage. In addition, because nerve impairment is responsible for the long-lasting neuropathic component of postoperative pain, it is necessary to match specific treatments to the neuropathic pain-generating mechanisms.

Case-Control Studies↗
PubMed1998

Patterns of mood variation during antidepressant treatment.

Previous findings showed that, in a subgroup of patients administered heterogeneous antidepressant treatments, perceived mood levels during a major depressive episode fluctuate with day to day changes which follow cyclical patterns (termed "minicycles"). We investigated the predictability of infradian mood fluctuations during acute depressive episodes in patients standardly medicated with fluvoxamine. We applied time series analysis, by means of autocorrelation techniques, to time lagged serial recordings of perceived mood levels of 20 inpatients (13 Major Depression Recurrent, and 7 Bipolar Depressive Disorders). 5/20 patients exhibited predictable cyclical patterns in their perceived symptomathology, 8/20 exhibited an uneven, sawtooth pattern of progressive amelioration, and 7/20 showed an erratic pattern of unpredictable day-to-day variations. We confirmed the existence and the predictability of cyclical mood patterns in a subgroup of patients. The absence of a linear improvement in perceived mood did not worsen the final response to antidepressant therapy.

Antidepressive Agents, Second-Generation↗
PubMed1998

Dose-response relationship of opioids in nociceptive and neuropathic postoperative pain.

The treatment of neuropathic pain with opioid analgesics is a matter of controversy among clinicians and clinician scientists. Although neuropathic pain is usually believed to be only slightly responsive to opioids, several studies show that satisfactory analgesia can be obtained if adequate doses are administered. In the present study, we tested the effectiveness of buprenorphine in 21 patients soon after thoracic surgery (nociceptive postoperative pain) and 1 month after surgery in the same 21 patients who developed postthoracotomy neuropathic pain with a burning, electrical and shooting quality. According to a double-blind randomized study, the analgesic dose (AD) of buprenorphine needed to reduce the long-term neuropathic pain by 50% (AD50) was calculated and compared to the AD50 in the immediate postoperative period. We found that long-term neuropathic pain could be adequately reduced by buprenorphine. However, the AD50 in neuropathic pain was significantly higher relative to the AD50 in the short-term postoperative pain, indicating a lower responsiveness of neuropathic pain to opioids. We also found a strict relationship between the short-term and long-term AD50, characterized by a saturating effect. In fact, if the AD50 soon after surgery was low, the AD50 increase in the long-term neuropathic pain was threefold. By contrast, if the AD50 soon after surgery was high, the AD50 in neuropathic pain was only slightly increased. This suggests that, though neuropathic pain is indeed less sensitive to opioids, in some neuropathic patients a large amount of opioid resistance is already present in other painful conditions.

Aged↗
PubMed1998

The specific effects of prior opioid exposure on placebo analgesia and placebo respiratory depression.

Although in most of the cases the placebo response appears to be unpredictable, several factors have been considered in order to explain the placebo analgesic effect. For example, it is widely recognized, albeit with little empirical evidence, that placebo analgesia is more likely to occur after a successful analgesic therapy. On the basis of this assumption, we tested the placebo response in a population of patients who were treated with buprenorphine the day before for relieving postoperative pain. However, due to the high variability of opioid responsiveness, buprenorphine was effective in some patients and poorly effective in some others. Similarly, buprenorphine produced respiratory depression with a large variability, ranging from mild depression to no effect. We found that the placebo analgesic response depended on the buprenorphine analgesic effectiveness of the previous day. Analogously, we found that a placebo respiratory depressant response was more pronounced in those patients with a respiratory depressant response to buprenorphine on the day before, irrespective of the analgesic effectiveness. These specific effects suggest that (1) the placebo effect is experience-dependent; (2) the mechanisms underlying placebo analgesia and placebo respiratory depression are independent from each other and, by considering the role of endogenous opioids in placebo analgesia, might involve different subpopulations of opioid receptors.

Analgesia↗
PubMed1998

Transmission of an anti-RhD alloantibody from donor to recipient after ABO-incompatible BMT.

We report a bone marrow transplant which was HLA matched, with major and minor ABO and minor RhD incompatibility (anti-RhD antibody) between the donor and recipient. When engraftment occurred, the recipient developed an anti-RhD antibody of donor origin detected by direct and indirect antiglobulin tests (DAT, IAT) and showed signs of mild hemolytic anemia. With the disappearance of the recipient RBCs, the DAT became negative and the hemolysis disappeared, while the anti-RhD alloantibody persisted in the patient's serum. This case emphasizes the importance of close immuno-hematological monitoring in patients undergoing allogeneic BMT with ABO-RhD incompatibility between recipient and donor.

ABO Blood-Group System↗
PubMed1998

Clinical study of 9-cis retinoic acid (LGD1057) in acute promyelocytic leukemia.

The use of all-trans retinoic acid (RA) for remission induction markedly increases survival of patients with acute promyelocytic leukemia (APL) compared to patients treated solely with cytotoxic chemotherapy. However, clinical resistance to this agent develops rapidly, which has been associated with a progressive decline in plasma drug concentrations. Previous studies suggested that 9-cis RA, a retinoid receptor 'pan agonist' did not induce its own catabolism to the same extent as all-trans RA. Therefore, we conducted a dose-ranging study of this compound in patients with both relapsed and newly diagnosed APL. We treated 18 patients with morphologically diagnosed APL (13 relapsed, five newly diagnosed). The daily dose of 9-cis RA ranged from 30 to 230 mg/m2/day given as a single oral dose. Four of 12 (33%) relapsed patients (three of whom were previously treated with all-trans RA) and four of five (80%) newly diagnosed patients achieved complete remission. The sole failure in the newly diagnosed group died early from an intracranial hemorrhage. One other patient with t(9;12) translocation had substantial hematologic improvement. The drug was generally well tolerated; headache and dry skin were the most common adverse reactions. Three patients were treated with corticosteroids for signs of incipient 'RA syndrome.' These preliminary data suggest that 9-cis RA is an effective agent for remission induction and deserves further investigation in patients with retinoid-sensitive APL.

Adolescent↗
PubMed1998

Polymorphism within the promoter of the serotonin transporter gene and antidepressant efficacy of fluvoxamine.

Depression with psychotic features has been shown to respond to selective serotonin reuptake inhibitors (SSRIs). The serotonin transporter (5-HTT) is a prime target for SSRIs. A functional polymorphism within the promoter region of the 5-HTT gene, leading to different transcriptional efficiency, was recently reported. We tested the hypothesis that allelic variation of the 5-HTT promoter could be related to the antidepressant response to fluvoxamine and/or augmentation with pindolol (a serotonin autoreceptors antagonist) which has been suggested as an augmentation therapy for nonresponders. One hundred and two inpatients with major depression with psychotic features were randomly assigned to treatment with a fixed dose of fluvoxamine and either placebo or pindolol for 6 weeks. Depression severity was assessed once a week using the Hamilton Depression Rating Scale. Allelic variation in each subject was determined using a PCR-based method. Data were analyzed with a three-way repeated measures analysis of variance. Both homozygotes for the long variant (l/l) of the 5-HTT promoter and heterozygotes (l/s) showed a better response to fluvoxamine than homozygotes for the short variant (s/s). In the group treated with fluvoxamine plus pindolol all the genotypes acted like l/l treated with fluvoxamine alone. Fluvoxamine efficacy in delusional depression seems to be related to allelic variation within the promoter of the 5-HTT gene. Even though other factors may be implicated, genotyping at 5-HTT promoter may represent a promising tool to individualize the pharmacological treatment of depression.

Antidepressive Agents, Second-Generation↗
PubMed1998

Low-dose clozapine in acute and continuation treatment of severe borderline personality disorder.

BACKGROUND: Psychotic-like symptoms in patients affected by borderline personality disorder (BPD) are usually treated with low-dose neuroleptics, which show controversial acute effects and lead to a worsening of affective-related symptoms and to severe neurologic side effects after prolonged administration. Clozapine lacks the neurologic side effects of traditional neuroleptics and has been shown to successfully treat psychotic-like symptoms in BPD patients at medium dose. We performed an open-label trial of low-dose clozapine in severe BPD patients. METHOD: Twelve BPD inpatients (DSM-IV criteria) with severe psychotic-like symptoms were studied. Exclusion criteria included comorbid Axis I and medical pathologies. All patients had followed a therapeutic program without improvement for at least 4 months before admission. The clozapine dose was titrated upward on an individual basis until the complete disappearance of psychotic-like symptoms was achieved. Clinician-rated scales were completed at the beginning of the study and after 4 and 16 weeks. RESULTS: All patients completed the 16-week study. Individual clozapine doses ranged from 25 to 100 mg/day. Psychotic-like symptoms decreased within the first 3 weeks of treatment, as confirmed by a statistically significant decrease in Brief Psychiatric Rating Scale scores. This amelioration was coupled with an overall improvement, including a reduction in impulsive behaviors and in affective-related symptoms (Hamilton Rating Scale for Depression) and an increase in global functioning (Global Assessment of Functioning). CONCLUSION: Low-dose clozapine for acute and continuation treatment led to improvement in overall symptomatology in a small sample of severe BPD patients.

Adult↗
PubMed1997

Sleep deprivation hastens the antidepressant action of fluoxetine.

Among ten bipolar depressed patients admitted to our psychiatric ward, five patients were treated with fluoxetine alone and five subjects were treated with fluoxetine in association with total sleep deprivation (TSD) in order to evaluate the effect of the interaction between the administration of the serotonergic antidepressant compound fluoxetine and repeated cycles of TSD. Patients treated with fluoxetine plus repeated TSD showed a faster amelioration of depressive symptomatology compared with the other group. We discuss our findings hypothesizing an enhancement in dopaminergic and possibly in serotonergic transmission due to repeated TSD adding to the increase in serotonergic transmission due to fluoxetine medication.

Adult↗
PubMed1997

Control of postoperative pain by transcutaneous electrical nerve stimulation after thoracic operations.

BACKGROUND: Transcutaneous electrical nerve stimulation (TENS) has been used extensively to control postoperative pain, but its effects are controversial. This is probably due to the different types of operations performed and, therefore, to the varying intensity of postoperative pain. Here we present an extensive study with TENS in 324 patients who underwent different types of thoracic surgical procedures: posterolateral thoracotomy, muscle-sparing thoracotomy, costotomy, sternotomy, and video-assisted thoracoscopy. METHODS: Each patient cohort was randomly subdivided into three treatment groups: TENS, placebo TENS and control. The effectiveness of TENS was assessed by two factors: the time from the beginning of treatment to the request for further analgesia and the total medication intake during the first 12 hours after operation. RESULTS: Whereas posterolateral thoracotomy produced severe pain, muscle-sparing thoracotomy, costotomy, and sternotomy caused moderate pain, and video-assisted thoracoscopy caused only mild pain. The TENS treatment was not effective in the posterolateral thoracotomy group, but it was useful as an adjunct to other medications in the muscle-sparing thoracotomy, costotomy, and sternotomy groups. In contrast, representing the only pain control treatment with no adjunct drugs, it was very effective in patients having video-assisted thoracoscopy. CONCLUSIONS: These findings show that TENS is useful after thoracic surgical procedures only when postoperative pain is mild to moderate; it is uneffective for severe pain.

Endoscopy↗
PubMed1997

Postoperative pain and superficial abdominal reflexes after posterolateral thoracotomy.

BACKGROUND: Posterolateral thoracotomy can produce stretching of/or damage to the intercostal nerves and their branches. To assess intercostal nerve impairment after operation, we measured the superficial abdominal reflexes, which are mediated, at least in part, by the most inferior intercostal nerves. METHODS: Using electrophysiologic techniques, we made recordings from the left and right abdominal walls to study the responses evoked by mechanical stimulation of the skin after operation. In addition, we assessed postoperative pain intensity according to a numeric rating scale and recorded postoperative opioid dose. RESULTS: We found that the patients with complete disappearance of the superficial abdominal reflexes experienced more severe postoperative pain than those in whom the reflexes were maintained. Moreover, opioid treatment was less effective in the patients with no reflexes postoperatively. CONCLUSIONS: Our findings show a strict correlation between pain intensity after posterolateral thoracotomy and absence of abdominal reflexes. We suggest that the higher pain intensity together with the absence of reflexes may be due to intercostal nerve impairment, be it anatomic or functional, and thus to a larger neuropathic component of postoperative pain. This finding may be used as a predictor of patients with high analgesic requirements.

Electrophysiology↗