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Biomedical subjects

I Mancini

Publications and source records attributed to I Mancini.

At least 19 recordsLinked to original sources
PubMed2004

[Breast cancer treatment in 2004: towards a tailored approach].

Breast cancer remains one of the most frequent malignancies that general practitioners are confronted with. Given their key-counselling role for the affected families, they need regular updates on the multi-disciplinary management of the disease. This has been characterized by an evolution towards less aggressive surgery, sparing many women the morbidity of a full axillary node dissection; in parallel, there is increasing hope for "individualized" adjuvant medical treatment, given the development of new technologies that provide an "identity card" of the genes expressed by each tumour. These technologies should improve our ability to identify which women truly need adjuvant chemotherapy and to select the best medical treatment on an individual basis. While providing these messages of hope, this chapter also reviews the major classes of drugs used for the treatment of advanced breast cancer.

Breast Neoplasms↗
PubMed2003

Is a cooled tip catheter the solution for the ablation of the cavotricuspid isthmus?

To test the theoretical superiority of irrigated tip catheters to achieve complete cavotricuspid isthmus block, a 4-mm cooled tip catheter was compared to a conventional 8-mm tip catheter with a double temperature sensor in the cavotricuspid isthmus (CTI) ablation. The study prospectively enrolled 60 patients (47 men, mean 65 +/- 10 years) with common flutter divided in group 1 (n = 30) assigned to an 8-mm tip catheter versus group 2 (n = 30), assigned to an internal circuit, irrigated tip catheter. Linear radiofrequency applications were performed in a point-by-point protocol to achieve complete CTI block. Complete CTI block was achieved in 29 patients in each group. Mean durations of procedure and fluoroscopy were 91 versus 90 and 40 versus 33 minutes in group 1 versus 2, respectively, (NS). The mean number/patient of RF pulses to interrupt atrial flutter was four in group 1 and eight in group 2 (P = 0.034), and 11 and 13, respectively, to interrupt CTI conduction (NS). The total energy delivered was similar in both groups (29,237 vs 23,236 W/s, NS). CTI ablation with a conventional 8-mm tip catheter versus an irrigated tip catheter was associated with similar success rates, procedure duration, and fluoroscopic exposure. The technical complexity of the cooled tip catheter renders it less competitive.

Adult↗
PubMed2002

Supportive and palliative care: experience at the Institut Jules Bordet.

The Supportive and Palliative Care Unit of the Institut Jules Bordet officially started its activities in February 1999. Our Unit comprises eight beds (four rooms with one bed each and two rooms with two beds each). We admit advanced cancer patients presenting with severe symptoms whose control is going to require all the expertise of a multidisciplinary team. Whilst these eight beds are identified geographically in the hospital, the team's mobility assures continuity of care for patients who wish to stay in another department. The infrastructure of the Unit and its rooms allow close family members who wish to sleep close to the patients to do so. Otherwise, visits are allowed round the clock, though always with due consideration for patients' comfort. Patients are referred either by a physician working in our Institution (medical oncologist, surgeon, or radiotherapist) or by their family physicians. Less frequently, patients themselves specifically ask to be admitted to our Unit. The activity of the Unit itself during its first year of functioning can be summarized as follows. We admitted 155 advanced cancer patients, for a total number of 210 hospitalizations. Patients were admitted a median of 35 months after their diagnosis and a median of 20 days before death. Stays were generally short (median 11 days). We systematically used quantitative assessment tools (MMSQ, MDAS,EFAT and various VAS) to detect and monitor their symptoms and any complications. The main symptoms on admission were pain, anorexia, asthenia, dyspnea and anxiety/depression. Pain, nausea/vomiting, constipation and cough were controlled in almost all patients, whereas control of asthenia and anorexia was most often insufficient. In 51% of our cases the patients could be discharged home; 40% died in the unit; 4% were transferred to long-term palliative care units and 1% to other units within our Institution (4% were still hospitalized at the time of this analysis).

Adult↗
PubMed2001

Bisphosphonates for cancer patients: why, how, and when?

Bisphosphonates (BPs) are potent inhibitors of osteoclast-mediated bone resorption, and it is well accepted that tumor cells in bone, especially breast cancer and myeloma cells, can stimulate osteoclast formation and activity leading to the release of growth factors or cytokines, which will further stimulate cancer cells' growth and their secretion of osteolytic factors. BPs are now the standard treatment for cancer hypercalcemia, for which a dose of 90 mg of pamidronate or 1500 mg of clodronate is recommended; the former compound is more potent and has a longer lasting effect. Repeated pamidronate infusions exert clinically relevant analgesic effects in more than half of patients with metastatic bone pain. Recent data suggest that non-responding patients should perhaps be treated with higher doses. The optimal dose actually remains to be defined, especially as it is thought that it is probably a function of the disease stage. Regular pamidronate infusions can also achieve a partial objective response according to conventional UICC criteria and they can almost double the objective response rate to chemotherapy. Lifelong administration of oral clodronate to patients with breast cancer metastatic to bone reduces the frequency of morbid skeletal events by more than one-fourth. Two double-blind randomized placebo-controlled trials comparing monthly 90 mg pamidronate infusions to placebo infusions for 1-2 years in addition to hormone or chemotherapy in patients with at least one lytic bone metastasis have shown that the mean skeletal morbidity rate could be reduced by 30-40%. The results obtained with intravenous BPs are generally viewed as better than those obtained with oral clodronate. However, preference can be given to the oral route when BPs are started early in the process of metastatic bone disease in a patient receiving hormone therapy. According to the recently published ASCO guidelines, pamidronate 90 mg i.v. delivered over 2 h every 3-4 weeks can be recommended in patients with metastatic breast cancer who have imaging evidence of lytic destruction of bone and who are concurrently receiving systemic therapy with hormonal therapy or chemotherapy. Furthermore, the ASCO Panel considered it "reasonable" to start i.v. BPs in women with localized pain whose bone scans were abnormal and plain radiographs normal, but not when an abnormal bone scan is asymptomatic. The pertinence of these criteria is discussed below. Because BPs are providing supportive care, reducing the rate of skeletal morbidity but evidently not abolishing it, the criteria for stopping their administration have to be different from those used for classic antineoplastic drugs, and they should not be stopped when metastatic bone disease is progressing. However, criteria to determine whether and for how long an individual patient benefits from their administration are lacking. New biochemical markers of bone resorption might help identify those patients continuing to benefit from therapy. Even better results have been achieved in patients with multiple myeloma, and the general consensus is that BPs should be started as soon as the diagnosis of lytic disease is made in myeloma patients. On the other hand, data are scanty in prostate cancer, but large-scale trials with potent BPs are ongoing or planned in such patients. Similar results to those achieved with pamidronate have been obtained with monthly 6-mg infusions of the newer BP ibandronate in patients with breast cancer metastatic to bone. The tolerance of ibandronate could be better, and the drug has the potential to be administered as a 15- to 30-min infusion. Zoledronate can also be administered safely as a 15-min 4-mg infusion, and large scale phase III trials have just been completed. These newer BPs will simplify the current therapeutic schemes and improve the cost-effectiveness ratio; they also have the potential to improve the therapeutic efficacy, at least in patients with an aggressive osteolytic disease or when given as adjuvant therapy. For that matter, initial data with clodronate indicate that they have the potential to prevent the development of bone metastases, but the use of BPs in the adjuvant setting must still be viewed as experimental.

Bone Neoplasms↗
PubMed2001

Antibacterial and anticholinesterase activities of aplysamine-4, a bromotyrosine-derived metabolite of a Red Sea marine sponge.

Aplysamine-4, a metabolite of likely bromotyrosine biogenesis, was isolated from an unidentified verongid sponge from the Red Sea. The compound was identified by heteronuclear magnetic resonance experiments, and by electrospray ionization tandem mass spectrometry. The compound exhibited moderate inhibitory activity on several Gram positive and Gram negative bacteria, and was also found to be a non-competitive reversible inhibitor of acetylcholinesterase. At pH 7.4, a Ki value of 16 and 2 microM was determined with electric eel and insect recombinant acetylcholinesterase, respectively. A deprotonated form of aplysamine-4 was obtained by alkaline treatment of the natural compound and it was shown to be less active than the protonated form.

Animals↗
PubMed2000

Molecular characterization of a highly heterogeneous mixture of glucosylceramides from a deep-water Mediterranean scleractinian coral Dendrophyllia cornigera.

We report here on the structural characterization of a highly heterogeneous mixture of glucosylceramides (GlcCers) isolated from a deep-water Mediterranian dendrophylliid coral, Dendrophyllia cornigera. The neutral glycosphingolipid (GSL) components of the coral were separated into three HPLC fractions which were structurally characterized by nuclear magnetic resonance (NMR) and mass spectrometry (MS). NMR analysis revealed a beta-glucosylpyranose, a methyl branched conjugated sphingadienine and alpha-hydroxy fatty acid moieties characteristic for the species. Molecular mass distributions of the HPLC fractions were monitored using single-stage MS. At least 17 different GlcCer constituents with variable long-chain base and fatty acid residues were observed based on the molecular ion peaks in the liquid secondary ion (LSI) survey spectra. Structures of the individual components were revealed by product ion spectra of the alkali-cationized molecules ([M + Cat](+)), which resulted in two characteristic fragment ions, F(F) and F(S). Tandem MS of the same fragment ions formed in the ion source showed that F(F) carries the hydoxy fatty acid, while F(S) carries the long-chain sphingoid base, thus providing complementary structural information for the characterization of ceramide composition. Based on the tandem mass spectra of the molecular ions [M + Na](+), 26 different GlcCers of the coral were identified. The ceramide moiety showed heterogeneity in both the sphingoid portion (d18:2, d19:2, d20:2 and d20:3) and the alpha-hydroxy fatty acid chain (h19-h24, either saturated or unsaturated), forming an extremely heterogeneous mixture. The method is generally applicable to the characterization of structurally heterogeneous GlcCer mixtures.

Animals↗
PubMed2000

Opioid switch to oral methadone in cancer pain.

The occurrence of undesirable side effects due to opioids (delirium, confusion, myoclonus, nausea, emesis) is one of the major complications in the management of pain, especially in chronic cancer pain states. Methadone, as an alternative to morphine, has been proposed in the control of opioid-induced toxicity. Methadone is a synthetic opioid, with mu and delta receptor activity, associated with the capacity to inhibit N-methyl-D-aspartate receptors. Questions have arisen concerning its equianalgesic ratio since its rediscovery over the past few years and are certainly related to its receptor interactions. Aspects of its pharmacology, indications, and switching modalities are discussed here. Opioid rotation is a new tool in the management of cancer pain, deserving more attention.

Administration, Oral↗
PubMed2000

Sedation for delirium and other symptoms in terminally ill patients in Edmonton.

The use of sedation and the management of delirium and other difficult symptoms in terminally ill patients in Edmonton has been reported previously. The focus of this study was to assess the prevalence in the Edmonton region of difficult symptoms requiring sedation at the end of life. Data were collected for 50 consecutive patients at each of (a) the tertiary palliative care unit, (b) the consulting palliative care program at the Royal Alexandra Hospital (acute care), and (c) three hospice inpatient units in the city. Patients on the tertiary palliative care unit were significantly younger. Assessments confirmed the more problematic physical and psychosocial issues of patients in the tertiary palliative care unit. These patients had more difficult pain syndromes and required significantly higher doses of daily opioids. Approximately 80% of patients in all three settings developed delirium prior to death. Pharmacological management of this problem was needed by 40% in the acute care setting, and by 80% in the tertiary palliative care unit. The patients sedated varied from 4% in the hospice setting to 10% in the tertiary palliative care unit. Of the 150 patients, nine were sedated for delirium, one for dyspnea. The prevalence of delirium and other symptoms requiring sedation in our area is relatively low compared to others reported in the literature. Demographic variability between the three Edmonton settings highlights the need for caution in comparing results of different palliative care groups. It is possible that some variability in the use of sedation internationally is due to cultural differences. The infrequent deliberate use of sedation in Edmonton suggests that improved management has resulted in fewer distressing symptoms at the end of life. This is of benefit to patients and to family members who are with them during this time.

Aged↗
PubMed1999

Assessment of dyspnea in advanced cancer patients.

Dyspnea, which has been defined as an "uncomfortable awareness of breathing," is a frequent and devastating symptom in advanced cancer patients. It has been reported to occur in 21-79% of patients evaluated a few days or weeks before death. In advanced cancer, the aim of effective management is to minimize the patient's perception of breathlessness, which depends in turn on a reliable assessment. Unfortunately, most of our knowledge and experience of dyspnea has been acquired through working with patients with chronic pulmonary disease, and there is a dearth of literature relating specifically to the assessment of dyspnea in advanced cancer. Dyspnea is a complex sensation including several dimensions, such as antecedents (physiological and psychological events or stimuli preceding the development of dyspnea), mediators (characteristics of individuals or their environment affecting the response), reactions to dyspnea, and consequences or outcomes that result once the individual has reacted to a stimulus. The literature gives us many tools to measure these aspects. For example, antecedents may be assessed by the British Medical Research Council Questionnaire, the American Thoracic Questionnaire (ATS-DLD-78) and the Dyspnea Interview Schedule. Mediators of dyspnea may be measured by the ATS-DLD-78, the Chronic Respiratory Questionnaire (CRQ), the Dyspnea Interview Schedule, the Pulmonary Functional Status Scale (PFSS) and the Therapy Impact Questionnaire (TIQ). Reactions to dyspnea may be assessed by the Dyspnea Visual Analogue Scale (DVAS), the TIQ and the Borg Scale, and the consequences of it by the TIQ, the Baseline Dyspnea Index (BDI), the Transition Dyspnea Index (TDI), and CRQ, and by the Oxygen Cost Diagram (OCD), the Dyspnea Interview Schedule and the Modified Medical Research Council Dyspnea Scale (MRC). No single assessment tool considers all the different components of dyspnea, and the final choice will depend on the purpose of the assessment, taking into account that the provision of quality of life is of paramount importance to patients who have limited time left to them and that the assessment should not therefore detract from the quality of life by being overlong, complicated or invasive.

Dyspnea↗
PubMed1999

Molecular and cellular basis of the altered immune response against arsonate in irradiated A/J mice autologously reconstituted.

The humoral immune response to arsonate (Ars) in normal A/J mice is dominated in the late primary and particularly in the secondary response by a recurrent and dominant idiotype (CRIA) which is encoded by a single canonical combination of the variable gene segments: VHidcr11-DFL16.1-JH2 and Vkappa10-Jkappa1. Accumulation of somatic mutations within cells expressing this canonical combination or some less frequent Ig rearrangements results in the generation of high-affinity antibodies. By contrast, in partially shielded and irradiated A/J mice (autologous reconstitution) immunized with Ars-keyhole limpet hemocyanin (KLH), both the dominance of the CRIA idiotype and the affinity maturation are lost, whereas the anti-Ars antibody titer is not affected. To understand these alterations, we have analyzed a collection of 27 different anti-Ars hybridomas from nine partially shielded and irradiated A/J mice that had been immunized twice with Ars-KLH. Sequence analysis of the productively rearranged heavy chain variable region genes from those hybridomas revealed that (i) the canonical V(D)J combination was rare, (ii) the pattern of V(D)J gene usage rather corresponded to a primary repertoire with multiple gene combinations and (iii) the frequency of somatic mutations was low when compared to a normal secondary response to Ars. In addition, immunohistological analysis has shown a delay of 2 weeks in the appearance of full blown splenic germinal centers in autoreconstituting mice, as compared to controls. Such a model could be useful to understand the immunological defects found in patients transplanted with bone marrow.

Amino Acid Sequence↗
PubMed1998

Constipation in advanced cancer patients.

Constipation is a frequent, distressing, and underestimated complication in patients with advanced cancer. It may develop from general disturbances that may or may not be cancer related, but the use of opioids is one of the main causes in this population. Opioids affect the intestine by reducing motility and secretions and by increasing fluid absorption and blood flow. Untreated constipation may lead to several complications. Effective management of constipation starts with a careful assessment of the patient, including the history of the frequency and difficulty of defaecation, symptoms caused by constipation, and physical and rectal examinations. When the diagnosis of constipation is unclear, an abdominal X-ray may be required. The treatment of constipation includes general interventions, such as the availability of comfort and privacy or the elimination of medical factors that may contribute to constipation, and therapeutic interventions including oral or rectal laxatives and the use of prokinetic drugs and naloxone. The purpose of this paper is to review the pathophysiology and causes of constipation and the effects of opioids on the gastrointestinal tract, and to propose an approach for its assessment and management. Randomized clinical trials between different laxatives and/or prokinetic agents in cancer patients are needed, and future studies should focus on the validation of different clinical assessment tools for constipation.

Constipation↗
PubMed1998

Quinolones from a bacterium and tyrosine metabolites from its host sponge, Suberea creba from the Coral Sea.

A marine bacterium, identified as a pseudomonad, isolated from Suberea creba Bergquist, 1995 (Porifera, Dictyoceratida, Verongida, Aplysinellidae) collected along the eastern coast of New Caledonia, gave in culture phenazine-alpha-carboxamide, 2-n-heptylquinol-4-one, 2-n-nonylquinol-4-one, 2-n-(1'E-nonenyl)quinol-4-one, 3-n-heptyl-3-hydroxyquinolin-2,4-dione, a N-oxide-2-n-heptylquinoline derivative, and a benzyldiketopiperazine. None of these products could be detected, at the HPLC-UV sensitivity level, in the sponge extracts, which contained instead (+)-aerothionin, homoaerothionin, (+)-aeroplysinin-1, dibromo-, bromochloro-, and dichloroverongiaquinol. 2-n-Heptylquinol-4-one, (+)-aeroplysinin-1, and dibromoverongiaquinol showed strong antibacterial activity in vitro. The latter also proved promising for mariculture, rivaling chloramphenicol as an antibacterial agent in cultures of Pecten maximus larvae, while being nontoxic according to the Artemia salina test.

Journal Article↗
PubMed1998

[Treatment of cancer pain: the role of co-analgesics].

Opioid analgesics are widely acknowledged as the most important drugs for the treatment of chronic cancer pain. Although these drugs can in most cases control severe pain, even when they are used appropriately, they may produce new symptoms or exacerbate preexisting symptoms, most notably nausea and somnolence. The combination of severe pain, anorexia, chronic nausea, asthenia, and somnolence is a frequent finding in patient with advanced cancer. An adjuvant drug should meet at least one of the following criteria: 1) to increase the analgesic effect of opioids; 2) to decrease their toxicity; 3) to improve others symptoms associated with terminal cancer. Many drugs, such as nonsteroidal antiinflammatory agents, tricyclic antidepressants, corticosteroids, benzodiazepines, amphetamines, antiemetics, oral local anesthetics and bisphosphonates have been suggested to have adjuvant analgesic effects. Unfortunately, most of the evidence for the effects of these drugs is anedoctal. Controlled clinical trials are badly needed to precise the indications and the risk/benefit ratios of these agents, some of which have significant toxicity and could potentially aggravate narcotics toxicity.

Analgesics, Opioid↗
PubMed1998

[Nutritional and digestive disorders in palliative care].

The anorexia-cachexia syndrome is a particularly frequent complication of advanced cancer. Parenteral nutrition must remain the exception in palliative medicine but enteral nutrition through feeding tubes or by a gastrostomy is an efficient method to provide an adequate long term nutritional support at home which can improve the quality of life of the palliative care patient. One must never forget all simple means to improve nutritional status. Since the cost benefit ratio of the medications stimulating the appetite, such as the corticosteroids and the progestatives, must still be demonstrated in palliative medicine. Hiccups therapy is essentially based on several non pharmacological means and on the administration of metoclopramide, antacids, haloperidol or chlorpromazine. Chronic nausea is an extremely frequent problem in palliative care, treated most often by metoclopramide, haloperidol and corticosteroids. Constipation is another extremely frequent problem which can lead to serious complication if left untreated. Besides general means, therapeutic means essentially comprise drugs such as lactulose and macrogol, bisacodyl, docusan and prokinetic agents like cipraside.

Gastrointestinal Diseases↗
PubMed1998

[Hypodermoclysis, a neglected approach].

Patients with advanced cancer frequently present with chronic nausea, emesis, bowel obstruction, confusional syndromes or dysphagia. All these conditions make it difficult for the patient to take oral medications or to maintain an adequate level of hydration by mouth. Hypodermoclysis is a safe and simple method that allows for cost-effective sucutaneous delivery of fluids and drugs. Hypodermoclysis has some clearcut advantages over the i.v. route. It can be started without need for a physician or a nurse, does not immobilize a limb, can be stopped and restarted at any moment without concern for clotting, and its use sparses nursing time. It also allows for easier and safer home discharge. Potentiel side effects of hypodermoclysis include pain at infusion site, sloughing tissues as a result of insufficient fluid absorption, infection, and puncture of vessels with bleeding. This paper gives some guidelines for the use of hypodermoclysis for fluid, electrolytes and drugs frequently used in a palliative care setting. The controversy surrounding the treatment of dehydration in the terminally ili is also briefly examined.

Algorithms↗