Imatinib therapy for chronic myeloid leukemia patients who relapse after allogeneic stem cell transplantation: a molecular analysis.
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Adult↗
Biomedical subjects
F Benedetti
Publications and source records attributed to F Benedetti.
Placebo and endogenous mechanisms of analgesia.
The discovery of the endogenous systems of analgesia has produced a large amount of research aimed at investigating their biochemical and neurophysiological mechanisms and their neuroanatomical localization. Nevertheless, the neurobiological acquisitions on these mechanisms have not been paralleled by behavioural correlates in humans--in other words, by the understanding of when and how these endogenous mechanisms of analgesia are activated. Until recent times one of the most studied behavioural correlates of endogenous analgesia was stress-induced analgesia, in which the activation of endogenous opioid systems is known to be involved. By contrast, today the placebo analgesic effect represents one of the best-described situations in which this endogenous opioid network is naturally activated in humans. Therefore, not only is placebo research helpful towards improving clinical trial design and medical practice, but it also provides us with a better understanding of the endogenous mechanisms of analgesia.
Analgesia↗
Prolonged survival and low incidence of late toxic sequelae in advanced follicular lymphoma treated with a TBI-free autografting program: updated results of the multicenter consecutive GITMO trial.
This study provides an updated report of the consecutive multicenter Gruppo Italiano Trapianto Midollo Osseo trial employing an intensified, purging-free, total body irradiation-free, high-dose sequential chemotherapy schedule with peripheral blood stem cell autograft (i-HDS) in advanced-stage follicular lymphoma (FL). Special interest has been devoted to late toxicities and outcome in terms of molecular status. Ninety-two untreated FL patients aged <or=60 were enrolled by 20 Italian centers and evaluated on an intention-to-treat basis. Main findings are as follows: (1) 5.5-years overall survival projection of 80% (median follow-up: 68 months), with no differences related to age-adjusted IPI score; (2) 46 (50%) of 92 patients presently in continuous complete remission; (3) projected long-term progression-free survival exceeding 80% for patients collecting PCR-negative stem cell harvests or achieving molecular remission within the first 2 years from the end of therapy; (4) actuarial 5-years risk of developing secondary myelodysplasia and acute myeloid leukemia of 3.7%, with most of these events occurring in patients re-treated for recurrent lymphoma. These results demonstrate that i-HDS is feasible, effective and safe even in terms of long-term outcome. As the HDS schedule can be easily supplemented with Rituximab, it is one of the best options for random comparison with Rituximab-supplemented conventional chemotherapy.
Adolescent↗
Placebo analgesia.
The placebo effect is the effect that follows the administration of an inert treatment (the placebo), be it pharmacological or not. It is important to understand that a placebo procedure simulates a therapy through the surrounding psychosocial context. Therefore, the study of the placebo effect is the study of the psychosocial context around the patient and its effects on the patient's brain. The real placebo response is a psychobiological phenomenon that can be due to different mechanisms, for example expectation and conditioning. Thus, there is not a single placebo effect but many, so that we have to look for different mechanisms in different conditions and in different systems and apparatuses. Today we are beginning to understand some of the neurobiological mechanisms of the placebo response, and this knowledge may help better understand the top-down control of the incoming sensory input, like pain, and the intricate interaction between mind and body.
Analgesia↗
[Gastric lipoma presenting as intestinal obstruction].
Gastric lipoma is a rare benign tumor. The symptoms are correlated with the size and the dimensions of neoplasm. It can be the cause of bleeding, gastroduodenal intussusception and intestinal obstruction, as in case reported and surgically treated. The Authors make a literature review to define the better diagnostic and surgical approach.
Diagnosis, Differential↗
[Strangulated abdominal herniation by Ladd's band].
A case of a 64-year-old man with abdominal pain since three days, with vomiting and ileus and without previous surgery is reported. Faecal material was aspirated by a nasogastric tube; TC showed dilatation of the small bowel with the walls of the loops thickened. The patient was submitted to emergency surgery with diagnosis of intestinal infarction. At laparotomy an extensive necrosis (two meters) of small bowel was present, caused by visceral herniation by a Ladd's band. Intestinal resection was performed with latero-lateral stapled anastomosis. The postoperative course was uneventful and the patient was transferred in VII p.o. day to an hospital of his Country.
Abdominal Pain↗
[Gangrene of Meckel's diverticulum in strangulated left inguinal hernia].
We report a case of a 57-year-old woman admitted for abdominal pain and a not reducible mass in left inguino-abdominal region. With a diagnosis of strangulated inguinal hernia, the patient underwent urgent surgery. The surgical exploration showed a gangrenous intestinal loop with a Meckel's necrotic diverticulum. A small bowel resection (20 cm) was performed. The post-operative course was uneventful. This seems the first case reported in the literature of woman with a Meckel's diverticulum involved in a strangulated left inguinal hernia.
Female↗
Does laparoscopic excision of endometriotic ovarian cysts significantly affect ovarian reserve? Insights from IVF cycles.
BACKGROUND: Residual ovarian function after laparoscopic excision of endometriotic ovarian cysts is a major and still unsolved topic. Ultrasonographic evaluation of ovarian response to ovulation stimulation represents a simple yet poorly employed tool to assess residual ovarian function after surgery. METHODS: Data from patients referred for IVF or ICSI between January 2001 and December 2002 were reviewed. Patients were included who previously underwent laparoscopic excision of a monolateral endometriotic ovarian cyst. The operated ovary and contralateral intact ovary were compared in terms of number of follicles with a mean diameter >15 mm at the time of hCG administration. Basal volume of the two ovaries before initiating stimulation was also compared. A paired Student's t-test was used to investigate differences between the two ovaries. RESULTS: In total, 32 patients and 46 cycles were identified. The mean (+/- SD) number of follicles >15 mm was 4.2 +/- 2.5 in the control ovary and 2.0 +/- 1.5 in the previously operated ovary (P < 0.001); this corresponded to a mean reduction of 53% (95% CI 35-72%) but did not seem to be related to the dimension of the excised ovarian cyst. The basal volume of the operated ovaries was also statistically significantly diminished, though this reduction was less relevant. CONCLUSIONS: Excision of endometriotic ovarian cysts is associated with a significant reduction in ovarian reserve. Further studies are required to clarify whether the damage is related to the surgical procedure or to the previous presence of a cyst.
Adult↗
Evaluation of risk of Parkinson's disease in a cohort of licensed pesticide users.
In the last two years, the environmental theory on the aetiology of Parkinson disease has acquired new data. From an experimental point of view, a new model of parkinsonism induced by rotenone, a diffuse insecticide, has been proposed, and in vitro studies have provided proof that several pesticides stimulate the formation of alpha-synuclein fibrils (one of the principal constituents of Lewy bodies). Moreover, a meta-analysis of all case-control studies so far performed showed a positive, statistically significant association between pesticide exposure and PD. In this context, we are performing a cohort study on 5575 licensed pesticide users in the province of Viterbo. After 27 years of follow-up, 4788 subjects are still alive. The aim of this study is to measure the prevalence of Parkinson's disease in a large group of workers with theoretically increased risk.
Cohort Studies↗
Decreased sensitivity of 5-HT1D receptors in chronic tension-type headache.
OBJECTIVE: To assess the sensitivity of 5-HT1D receptors in chronic tension-type headache using sumatriptan as a pharmacological probe. BACKGROUND: Previous studies have suggested involvement of serotonergic systems in chronic tension-type headache (CTTH), but relevant experimental data are limited. Sumatriptan, a 5-HT1B/1D receptor agonist, stimulates the release of growth hormone (GH) and inhibits the release of ACTH, cortisol, and prolactin. These effects may be used to explore the function of serotonergic systems in vivo. METHODS: We measured GH, ACTH, cortisol and prolactin (PRL) plasma concentrations in 15 patients with chronic tension-type headache and in 18 healthy controls after subcutaneous administration of sumatriptan (6 mg) or placebo. RESULTS: Placebo administration had no effect on hormone concentrations. GH and PRL secretion after sumatriptan administration was significantly (P<0.01 and <0.05) altered in CTTH patients in comparison with controls. CONCLUSION: Our results suggest that cerebral serotonergic functions mediated by 5-HT1D receptors are altered in CTTH.
Adult↗
Serum levels of soluble CD30 improve International Prognostic Score in predicting the outcome of advanced Hodgkin's lymphoma.
BACKGROUND: The International Prognostic Score (IPS) and circulating levels of the soluble form of CD30 molecule (sCD30) have both been associated with poor outcome in patients with advanced Hodgkin's lymphoma (HL). The aim of this study was to assess the prognostic power of the combined evaluation of sCD30 and IPS in these patients. PATIENTS AND METHODS: We included 101 patients with advanced HL, treated with ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) or MOPP (mechlorethamine, vincristine, procarbazine and prednisone)/ABVD chemotherapy with or without radiotherapy. All were tested for pre-treatment sCD30 levels. RESULTS: Six-year estimated overall survival (OS) and failure-free survival (FFS) was 89% +/- 3% and 75% +/- 4%, respectively. Thirty-three patients (33%) had IPS >2; their FFS was 60% compared with 82% in the remaining patients (P = 0.027). Serum sCD30 levels were > or =100 U/ml in 41 (41%) patients; their FFS at 6 years was 58%, compared with 87% in patients with sCD30 <100 U/ml (P = 0.003). In the 18 patients with both sCD30 > or =100 U/ml and IPS >2, FFS was significantly worse (44%) than in patients with low sCD30 and low IPS (89%) (P <0.001) or with only one of the two adverse prognostic factors (73%) (P = 0.03). CONCLUSIONS: In our study, the combination of IPS >2 and serum sCD30 levels > or =100 U/ml identifies a sizeable subgroup (18%) of advanced HL patients with very poor FFS, who might take advantage of intensified up-front treatment strategies.
Adolescent↗
Dopaminergic augmentation of sleep deprivation effects in bipolar depression.
Total sleep deprivation (TSD) has been used in association with lithium salts and with serotonergic and noradrenergic antidepressants, leading to sustained improvements in patients affected by major depression. Current theories on the neurobiological mechanism of action of TSD propose a major role for enhanced dopamine activity. To test the clinical relevance of dopaminergic enhancement in TSD, we treated a homogeneous sample of 28 bipolar depressed patients with three cycles of TSD combined with placebo or with the dopaminergic antidepressant amineptine. Changes in mood over time were rated with self-administered visual analogue scales and with the Montgomery-Asberg Depression Rating Scale. Patients showed improved mean daily-mood scores after TSD, an effect that was highest at the first cycle and decreased with treatment repetition. Amineptine enhanced the effects of TSD on perceived mood during the first two TSD cycles, but patients in the placebo and amineptine groups showed comparable results at the end of the treatment. Despite its theoretical importance, the clinical usefulness of combining TSD with a dopaminergic agent must be questioned.
Bipolar Disorder↗
Phase I study of hepatic arterial infusion of floxuridine and dexamethasone with systemic irinotecan for unresectable hepatic metastases from colorectal cancer.
PURPOSE: To determine the maximum-tolerated dose (MTD) and dose-limiting toxicities of concurrent systemic irinotecan and hepatic arterial infusion (HAI) of floxuridine (FUDR) and dexamethasone in patients with unresectable hepatic metastases from colorectal cancer, to determine the safety of this combination in patients who have undergone cryosurgery, and to evaluate the pharmacokinetic effects of HAI FUDR on the metabolism of irinotecan. PATIENTS AND METHODS: Forty-six previously treated patients with unresectable liver metastases and no known extrahepatic disease were treated concurrently with intravenous irinotecan weekly for 3 weeks and with HAI of FUDR and dexamethasone for 14 days (both were recycled in 28 days). Parallel cohorts of patients treated with or without cryosurgery were entered at escalating dose levels. RESULTS: The MTD for patients who did not undergo cryosurgery was 100 mg/m2 of irinotecan weekly for 3 weeks every 4 weeks with concurrent HAI FUDR (0.16 mg/kg/d x pump volume/flow rate) plus dexamethasone for 14 days of a 28-day cycle. The dose-limiting toxicities were diarrhea and neutropenia. The response rate (complete and partial) among all patients who did not undergo cryosurgery was 74%. All patients in the cryosurgery group responded, and seven of the eight cryosurgery patients developed normal positron emission tomography scans after chemotherapy. HAI FUDR had no effect on the metabolism of irinotecan. CONCLUSION: Combination therapy with HAI FUDR and dexamethasone plus systemic irinotecan may be safely administered to patients with unresectable hepatic metastases from colorectal cancer. The MTD has been reached for patients with unresectable disease, and we continue to investigate the MTD for patients who have undergone cryosurgery. Although the main objective of this study was to evaluate the toxicity of the combined regimen, a high response rate (74%) was observed.
Adult↗
Morning sunlight reduces length of hospitalization in bipolar depression.
BACKGROUND: Bright artificial light improves non-seasonal depression. Preliminary observations suggest that sunlight could share this effect. METHODS: Length of hospitalization was recorded for a sample of 415 unipolar and 187 bipolar depressed inpatients, assigned to rooms with eastern (E) or western (W) windows. RESULTS: Bipolar inpatients in E rooms (exposed to direct sunlight in the morning) had a mean 3.67-day shorter hospital stay than patients in W rooms. No effect was found in unipolar inpatients. CONCLUSIONS: Natural sunlight can be an underestimated and uncontrolled light therapy for bipolar depression. LIMITATIONS: This is a naturalistic retrospective observation, which needs to be confirmed by prospective studies.
Adult↗
Unrelated allogeneic bone marrow donation: short- and long-term follow-up of 103 consecutive volunteer donors.
Between 1992 and 1999, 105 unrelated allogeneic bone marrow collections from 103 volunteer donors (65 males and 38 females; median age 33 years) were carried out in three northern Italian centers (Verona, Bolzano and Padova) affiliated with the Italian Bone Marrow Donor Registry (IBMDR). The average volume of BM collected was equivalent in both genders (1143.1 ml for males and 1054.2 ml for females; P = 0.1), although the average volume collected for unit of body weight and the average post-collection blood volume depletion was higher in females (respectively 17.1 ml/kg and 14.2% in females, 14.8 ml/kg and 12% in males; P= 0.01 and 0.03). There was no statistically significant difference between males and females in the total number of nucleated cells collected. We did not record any acute life-threatening event during or after the bone marrow collections. The most frequent complaint was pain at the collection site (77%) followed by the onset of fatigue (38%) and nausea and vomiting (25%); all of these were short-term problems. Hospitalization was short (average 20.2 h) and donors started their normal daily activities after an average of 5.4 days. We also monitored Hb, serum ferritin levels, WBC and platelet counts in the post-collection period (average follow-up 40.1 months). All donors signed a written informed consent for a further bone marrow collection, if needed. Our findings confirm the short- and long-term safety of allogeneic bone marrow collection in volunteer donors.
Adolescent↗
Intensification of salvage treatment with high-dose sequential chemotherapy improves the outcome of patients with refractory or relapsed aggressive non-Hodgkin's lymphoma.
The aim of the present study was to retrospectively evaluate whether a high-dose sequential chemotherapy programme (HDS: cyclophosphamide, methotrexate, etoposide) administered prior to autologous transplantation could optimize the salvage of patients with refractory or relapsed aggressive non-Hodgkin's lymphoma. Between 1985 and 1999, 103 patients (median age 43 years, range 16-65) from eight Italian centres and one Swiss centre, with refractory (n = 38) or relapsed (n = 65) diffuse large B-cell and T-cell lymphoma, were treated using HDS followed by high-dose regimens with autologous haematopoietic stem cell transplantation. Eighty-three patients responded to the HDS regimen (81%, 95% C.I., 73- 88%) and 79 eventually achieved a complete response (CR) after autotransplantation (90%, 95% C.I., 81- 96%). None of 20 cases resistant to HDS attained CR. Treatment-related mortality was 4%. After a median follow-up of 24 months (range 6-174 months), 3-year estimates of overall survival, event-free survival and disease-free survival were 47% (95% C.I., 36-59%), 44% (95% C.I., 34-54%) and 64% (95% C.I., 50-74%) respectively. Multivariate analysis showed that chemosensitivity to HDS represented the strongest predictor of both CR and survival. This retrospective study shows that salvage treatment using HDS had relatively low toxicity and was associated with remarkable response rates, allowing further effective therapy with high-dose autograft programmes.
Adolescent↗
Quantitative EEG responses to ischaemic arm stress in migraine.
Several studies suggest that patients with migraine respond physiologically to stress differently from controls, yet experimental data are scarce. In order to evaluate the reactivity to stress in migraine, we recorded the quantitative electroencephalogram (qEEG) during non-noxious and noxious ischaemic arm stress in two groups of healthy controls and compared the results with the effects of non-noxious ischaemic arm stress in a group of patients with migraine. In the controls, non-noxious mild stress did not produce any qEEG change but noxious stress induced a significant decrease of the alpha power. By contrast, in migraine patients the non-noxious mild stress was sufficient to induce a significant decrease of the alpha power in all brain regions. The results of our study show that migraine sufferers display a lower threshold to physical stress and confirm previous studies indicating that migraine is a disease characterized by a state of altered neuronal excitability.
Adult↗
Antidepressive response to sleep deprivation in unipolar depression is not associated with dopamine D3 receptor genotype.
The psychostimulant theory of antidepressive sleep deprivation (SD) proposes a contribution of dopamine D3 receptors (DRD3) in the limbic system to the antidepressant effects of SD. Neuroendocrinological studies suggest a positive correlation of clinical response to SD and cortisol secretion. We hypothesized that the clinical response to SD and amount of cortisol secretion upon SD is associated with the 1-1 genotype of the Bal1 polymorphism of DRD3 on exon 1. In this study, aiming at evaluating the feasibility of screening large patient samples, 52 inpatients (19 males/33 females) with unipolar depression and a score of 18 or more on the 21-item Hamilton Depression Rating Scale were treated with 1 night of total SD. We found that 31% of our patients responded to SD. There was no association between response to SD and the genotype of the DRD3 Bal1 polymorphism (p < 0.879). There was also no association between increase in cortisol secretion after SD and DRD3 genotypes (p < 1.000) in a subgroup of patients. Statistical power analysis ruled out a major effect of the DRD3 Bal1 polymorphism on clinical response to SD. These results suggest that the DRD3 Bal1 polymorphism is not a promising lead to be followed up in larger patient samples.
Adult↗