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M Sierra

Publications and source records attributed to M Sierra.

At least 19 recordsLinked to original sources
PubMed2006

Phase II study with the combination of gemcitabine and DTIC in patients with advanced soft tissue sarcomas.

PURPOSE: Based on the promising results of a Phase I study with a combination of gemcitabine and DTIC performed in advanced soft tissue sarcoma (ASTS) patients, and due to the limited efficacy of second or third line therapies in those patients, we designed a Phase II study to determine the activity of this new regimen. METHODS: Patients with ASTS, measurable disease, pretreated with chemotherapy, received gemcitabine 1,800 mg/m2 infused over 180 min followed by DTIC 500 mg/m2 (one cycle), every 2 weeks. The pharmacokinetics (PK) of gemcitabine and 2',2'-difluorodeoxyuridine (dFdU), and the accumulation of gemcitabine triphosphate (dFdCTP) by peripheral blood mononuclear cells were studied. The influence of the sequence of administration on those parameters was examined to exclude potential drug interactions. RESULTS: Twenty-six patients received a total of 158 cycles (mean four cycles, range 1-18). Grade 3-4 anemia (23% of patients), granulocytopenia (46%) or thrombocytopenia (12%), and grade 3 increase in AST (18%), ALT (21%), or gamma-glutamyl-transferase (9%) were noted. Response rate in 23 patients was 4% (95% CI: 0-24%), and in 8 of 11 patients stable disease lasted > 6 months. Progression-free rate (PFR) at 3 and 6 months was, respectively, 48 and 28%, and median overall survival 37 weeks. Pooled data from the Phase I and Phase II studies showed clinical benefit in patients with leiomyosarcomas (LMS) (57%) and malignant fibrous histiocytomas (MFH) (33%). The sequence of administration did not influence PK of gemcitabine or dFdU. There was a trend (P = 0.11) toward a lower accumulation of dFdCTP when DTIC preceded gemcitabine. CONCLUSIONS: Although the remission rate was low, PFR figures indicate that this regimen has activity in patients with ASTS. It should be compared with DTIC, or other gemcitabine-containing combinations, in patients with LMS or MFH, to determine whether this combination offers advantages in PFR or in overall activity.

Adult↗
PubMed2006

Phase I/II trial of doxorubicin and fixed dose-rate infusion gemcitabine in advanced soft tissue sarcomas: a GEIS study.

The aim of the study was to determine the dose-limiting toxicity and maximum tolerated dose of a first-line combination of doxorubicin and gemcitabine in adult patients with advanced soft tissue sarcomas and to explore its activity and toxicity, and the presence of possible interactions between these agents. Patients with measurable disease were initially treated with doxorubicin 60 mg m(-2) by i.v. bolus on day 1 followed by gemcitabine at 800 mg m(-2) over 80 min on days 1 and 8, every 21 days. Concentrations of gemcitabine and 2',2'-difluorodeoxyuridine in plasma, and gemcitabine triphosphate levels in peripheral blood mononuclear cells were determined during 8 h after the start of gemcitabine infusion. Myelosuppression and stomatitis were limiting toxicities, and the initial dose level was applied for the Phase II trial, where grade 3-4 granulocytopenia occurred in 70% of patients, grade 3 stomatitis in 46% and febrile neutropenia in 20%. Objective activity in 36 patients was 22% (95% CI: 9-35%), and a 50% remission rate was noted in leiomyosarcomas. Administration of doxorubicin preceding gemcitabine significantly reduced the synthesis of gemcitabine triphosphate. Clinical activity, similar to that of single-agent doxorubicin, and the toxicity encountered do not justify further studies with this schedule of administration.

Adult↗
PubMed2006

Isolated adrenal metastasis: the role of laparoscopic surgery.

BACKGROUND: Solitary adrenal metastases (AM) are rare and their management unclear. Surgery, especially laparoscopic adrenalectomy (LA), is debatable in the management of AM. This retrospective study analysed the feasibility and the results of LA for AM. METHODS: From 1997 to 2003, 16 patients underwent LA for isolated AM. Completeness of resection, postoperative morbidity and follow-up (FU) were recorded. RESULTS: There were 10 synchronous AM and 6 metachronous AM. Primary tumours included lung cancer (n = 9), melanoma (n = 3), mesothelioma (n = 1), rhabdomyosarcoma (n = 1), colonic adenocarcinoma (n = 1) and renal cell carcinoma (n = 1). Five patients required conversion to an open procedure. Minor complications occurred in three patients. Pathology confirmed the diagnosis of AM. Mean tumour size was 60 (range: 15-110) mm. Nine patients (56%) had complete resections, 3 had positive margins and 4 had incomplete macroscopic resections. Mean observed FU was 25 (range: 1-68) months. Median overall calculated survival was 23 months. Overall 5-year survival was 33% (Kaplan-Meyer). At the end of study, 8 patients were alive with a mean FU of 35 months (3 without evidence of disease). No patient presented with local relapse or port-site metastasis. We did not identify any predictive factors. All patients with incomplete macroscopic resection died within 24 months. CONCLUSIONS: LA can achieve an acceptable 5-year survival, comparable to open surgery but with better postoperative comfort. It should be considered for AM with the intention of complete resection. It offers the patient the possibility of tumour resection with the benefit of a laparoscopic approach.

Adrenal Gland Neoplasms↗
PubMed2006

Endoscopic lateral approach thyroid lobectomy: safe evolution from endoscopic parathyroidectomy.

INTRODUCTION: Endoscopic thyroid surgery has been shown to be feasible. Most minimal access procedures have been performed via a midline approach. Based on our experience of more than 500 endoscopic parathyroidectomies via a lateral approach we have used the same method for thyroid lobectomy. METHODS: We present our experience of endoscopic thyroid lobectomy via a lateral approach (ETLA) and review of the results over a 1-year period (2004). Inclusion criteria for ETLA were (1) solitary nodule with atypical/suspicious fine-needle biopsy (FNB) or solitary toxic nodule; (2) lesions with a diameter of < 3 cm. Patients with a history of previous neck surgery or radiation exposure were excluded. All patients underwent postoperative vocal cord checks and plasma calcium evaluation. RESULTS: A total of 742 thyroid procedures were performed during 2004. Among them, 38 patients (5.1%) underwent ETLA. Indications for surgery were suspicious FNB results (36 patients) and a toxic nodule (2 patients). Mean nodule size was 19.2 mm. Mean +/- SD operating time was 102 +/- 27 minutes. All recurrent laryngeal nerves were identified (including one that was nonrecurrent). Of the 38 patients, the superior parathyroid gland was identified in 36 and the inferior parathyroid gland in 33. There were two conversions due to difficulty with the dissection. Two operations were converted because malignancy was diagnosed on frozen section examination. Two patients underwent a delayed completion thyroidectomy when definitive histology necessitated it. There were no permanent operative complications, and all patients were discharged on the first postoperative day. CONCLUSIONS: ETLA offers excellent intraoperative visualization of the vital structures and is a safe alternative to conventional thyroid lobectomy in selected cases.

Adult↗
PubMed2005

[Abrikossoff tumor of the proximal esophagus misdiagnosed as a thyroid nodule].

The diagnosis of thyroid nodules is straightforward and rarely mistaken. We present a case of a paraesophageal granular cell tumor, discovered incidentally during surgery for what it was diagnosed as a suspicious thyroid nodule by ultrasound and FNA. Complete resection was achieved without disruption of the esophageal mucosa. A terminal branch of the recurrent laryngeal nerve had to be resected en bloc with the tumor. Morphological and immunohistochemical diagnosis was established postoperatively. A review of the literature is presented.

Adenocarcinoma↗
PubMed2005

Analysis of drug resistance-associated mutations in treatment-naïve individuals infected with different genetic forms of HIV-1 circulating in countries of the former Soviet Union.

There are few data on drug resistance-associated mutations in the former Soviet Union since, studies have usually been focused on the env or gag genes for subtype information. This study examines the prevalence and patterns of resistance-associated mutations to reverse transcriptase and protease inhibitors (RTI, PRI) in 278 HIV-1-infected treatment-naïve subjects from countries of Eastern Europe, and defines characteristic polymorphisms of RT and PR sequences in HIV-1 subtype A viruses. Blood samples were collected between 1997 and 2004. Plasma RNA was used for PR-RT amplification by reverse transcription coupled with nested PCR and sequencing. Phylogenetic analysis was done with neighbor-joining trees and bootscanning. Analysis of drug resistance mutations, with Stanford University HIV Drug Resistance Database's algorithm, resulted in an overall prevalence of 12.9% resistance to RTI and 3.9% to PRI. The most frequent substitutions in the RT region were at positions 62 and 236. V77I substitution in PR was found in 47.8% of samples. Polymorphisms in subtype A sequences were identified. This is the first study reporting the prevalence and patterns of both PRI and RTI resistance-associated mutations in naïve HIV-1 infected patients from the former Soviet Union. These data underline the importance of genotypic resistance testing of chronically HIV-1-infected patients before initiating treatment, in order to select the most suitable drug regimen.

Adult↗
PubMed2005

Natural resistance-associated mutations to Enfuvirtide (T20) and polymorphisms in the gp41 region of different HIV-1 genetic forms from T20 naive patients.

BACKGROUND: The natural occurrence of primary resistance mutations in reverse transcriptase (RT) and protease (PR) genes of HIV-1 isolates from untreated patients has been reported and it may have important implications for the response to drug treatment. It is predictable that the same occurs in the HR1 region of gp41 sequence from patients who have never received T20 therapy, and in this regard it would be important to know not only the mutation frequencies at HR1 region but also the natural polymorphisms at resistance-associated positions present in the absence of this drug. OBJECTIVES: The objectives of this study are to investigate the existence of natural resistance-associated mutations to T20 in HR1 gp41 region corresponding to different HIV-1 genetic forms from T20 naive patients and to determine their prevalence. STUDY DESIGN: Two hundred HIV-1 gp41 sequences were included: subtype B: 164 (81.3%); subtype A: 15 (8.2%); subtype G: 10 (4.6%); subtype F: 6 (3.5%); subtype C: 3 (1.8%); subtype K: 1 (0.6%); and subtype D: 1 (0.6%). We analyzed the resistance-associated mutations previously described: Q32H/R, G36D/S, I37V, V38A/M, Q39R/H, Q40H, N42T/D/Q/H, N43D/S/K/Q, L44M, L45M, R46M and V69I. RESULTS: Natural resistance mutations to T20 were found at a high frequency: 10.5%, corresponding to 9.1% in subtype B and 16.7% in non-B subtype samples. Polymorphisms were more frequent in non-B and recombinant forms than in subtype B (p<0.001). Different substitutions were related to subtypes: N42S in subtypes A, B, G and C, but not in F, Q56R in subtype A from CRF02_AG, and L54M in subtype B from CRF14_BG. CONCLUSIONS: To our knowledge this is the first study describing natural-resistance to T20 among different HIV-1 subtypes, warranting a study of the biological significance of this mutations and their clinical relevance. The detection of differences between subtypes may have an influence on the rate and patterns of resistance in patients undergoing T20 treatment.

Amino Acid Sequence↗
PubMed2004

Pneumococcal bacteremia in children: an 8-year review in two hospitals in Barcelona.

In this study, 90 episodes of pneumococcal bacteremia that occurred over an 8-year period in two hospitals in Barcelona were analyzed retrospectively to determine the clinical and bacteriological characteristics of pneumococcal bacteremia, the risk factors for antibiotic resistance, the outcome, and the vaccine coverage. The mean age of the patients was 3.1 years and the male/female ratio was 1.7. The overall rates of penicillin-non-susceptible, cefotaxime-non-susceptible, and erythromycin-resistant isolates were 48.8, 24.4, and 25.5%, respectively. Antibiotic resistance was associated with children under the age of 2 years and with previous antibiotic treatment. The percentage of antibiotic resistance was higher in the nine episodes that occurred in patients with an underlying illness. The most prevalent serotypes identified were 1, 14, 6B, 18C, 5, and 19A. Serotypes 6A/B, 14, and 19A/F were isolated primarily from children under 2, whereas serotypes 1 and 5 were recovered more frequently from older children. Apparent relationships between serotypes 6A/B, 14, and 19A/F and occult bacteremia and between serotypes 1 and 5 and bacteremic pneumonia were confounded by the age variable. The proportion of bacteremic episodes preventable by all (7-valent, 9-valent, and 11-valent) of the conjugate pneumococcal vaccines was 60% in children under 2. In older children, the serotype coverage rate for the three formulations was 48, 87, and 87%, respectively. In summary, these data expand upon previous Spanish studies in which serotypes 1 and 5 were reported to be among the leading causes of severe systemic pneumococcal infections in children over 2, findings that should be taken into consideration when planning vaccine programmes.

Adolescent↗
PubMed2004

The epidemiology of depersonalisation and derealisation. A systematic review.

BACKGROUND: Symptoms of depersonalisation (DP) and derealisation (DR) are increasingly recognised in both clinical and non-clinical settings, but their importance and underlying pathophysiology is only now being addressed. METHODS: This paper is a systematic review of the current state of knowledge about the prevalence of depersonalisation and derealisation using computerised databases and citation searches. All potential studies were examined and numerical data included. Three categories of study are reviewed: questionnaire and interview surveys of selected student and non-clinical samples; population-based community surveys using standardised diagnostic interviews; and clinical surveys of depersonalisation/derealisation symptoms occurring within inpatients with psychiatric disorders. In addition, we present newly analysed data of the prevalence of depersonalisation/derealisation from five large population-based studies. RESULTS: Epidemiological surveys demonstrate that transient symptoms of depersonalisation/derealisation in the general population are common, with a lifetime prevalence rate of between 26 and 74% and between 31 and 66% at the time of a traumatic event. Community surveys employing standardised diagnostic interviews reveal rates of between 1.2 and 1.7 % for one month prevalence in a UK sample and a 2.4% current prevalence rate in a Canadian sample. Current prevalence rates in samples of consecutive inpatient admissions are reported between 1 and 16%, although screening measures employed may have resulted in these being an underestimate. Prevalence rates in clinical samples of specific psychiatric disorders vary between 30% of war veterans with PTSD and 60% of those with unipolar depression. There is a high prevalence within panic disorder with rates varying from 7.8 to 82.6%. DISCUSSION: DP and DR symptoms are common in normal and psychiatric populations, but prevalence estimates are hampered by inconsistent definitions and the use of variable time-frames. Population-based surveys using diagnostic interviews yield prevalence rates of clinically significant DP/DR in the region of 1-2%. Surveys of clinical populations in which common screening and assessment instruments were used also yield consistently high prevalence rates. The use of reliable diagnostic assessments and rating scales is needed. The relationship between DP/DR and certain other psychiatric disorders (e. g. panic) suggests possible common pathophysiological or aetiological factors.

Adult↗
PubMed2003

Depersonalisation disorder: a cognitive-behavioural conceptualisation.

Depersonalisation (DP) and derealisation (DR) are subjective experiences of unreality in, respectively, one's sense of self and the outside world. These experiences occur on a continuum from transient episodes that are frequently reported in healthy individuals under certain situational conditions to a chronic psychiatric disorder that causes considerable distress (depersonalisation disorder, DPD). Despite the relatively high rates of reporting these symptoms, little research has been conducted into psychological treatments for this disorder. We suggest that there is compelling evidence to link DPD with the anxiety disorders, particularly panic. This paper proposes that it is the catastrophic appraisal of the normally transient symptoms of DP/DR that results in the development of a chronic disorder. We suggest that if DP/DR symptoms are misinterpreted as indicative of severe mental illness or brain dysfunction, a vicious cycle of increasing anxiety and consequently increased DP/DR symptoms will result. Moreover, cognitive and behavioural responses to symptoms such as specific avoidances, 'safety behaviours' and cognitive biases serve to maintain the disorder by increasing awareness of the symptoms, heightening the perceived threat and preventing disconfirmation of the catastrophic misinterpretations. A coherent model facilitates the development of potentially effective cognitive and behavioural interventions.

Adult↗
PubMed2002

Therapeutic effects of psyllium in type 2 diabetic patients.

OBJECTIVE: The aim of this study was to evaluate the effects of psyllium in type 2 diabetic patients. DESIGN: The study included three phases: phase 1 (1 week), phase 2 (treatment, 14 g fibre/day, 6 weeks) and phase 3 (4 weeks). At the end of each phase a clinical evaluation was performed after the ingestion of a test breakfast of 1824.2 kJ (436 kcal). Measurements included concentrations of blood glucose, insulin, fructosamine, GHbA(1c), C-peptide and 24 h urinary glucose excretion. In addition, uric acid, cholesterol and several mineral and vitamin concentrations were also evaluated. SETTING: The study was performed at the Department of Pharmacology, Toxicology and Nursing at the University of León (Spain). SUBJECTS: Twenty type 2 diabetic patients (12 men and 8 women) participated in the study with a mean age of 67.4 y for men and 66 y for women. The mean body mass index of men was 28.2 kg/m(2) and that of women 25.9 kg/m(2). RESULTS: Glucose absorption decreased significantly in the presence of psyllium (12.2%); this reduction is not associated with an important change in insulin levels (5%). GHbA(1c), C-peptide and 24 h urinary glucose excretion decreased (3.8, 14.9 and 22.5%, respectively) during the treatment with fibre (no significant differences) as well as fructosamine (10.9%, significant differences). Psyllium also reduced total and LDL cholesterol (7.7 and 9.2%, respectively, significant differences), and uric acid (10%, significant difference). Minerals and vitamins did not show important changes, except sodium that increased significantly after psyllium administration. CONCLUSIONS: The results obtained indicate a beneficial therapeutic effect of psyllium (Plantaben) in the metabolic control of type 2 diabetics as well as in lowering the risk of coronary heart disease. We also conclude that consumption of this fibre does not adversely affect either mineral or vitamin A and E concentrations. Finally, for a greater effectiveness, psyllium treatment should be individually evaluated.

Aged↗
PubMed2002

Separating depersonalisation and derealisation: the relevance of the "lesion method".

OBJECTIVES: Depersonalisation (DP) and derealisation (DR) are often met with in patients with a wide range of localisable neurological conditions. This suggests that the "lesion method" might be a valid approach to study the neurobiology of DP/DR. However, the fact that anxiety can trigger DP/DR makes it difficult to establish whether the presence of DP/DR in neurological patients is mainly determined by coexisting anxiety or by lesion location. To overcome this difficulty, we suggest the study of neurological phenomena, which although not considered as DP/DR, bear enough phenomenological resemblance with them as to warrant their use as models. METHODS: One patient with "visual hypoemotionality" and another with "hemiasomatognosia" are described in detail together with a selective literature review. RESULTS: Complaints of patients with visual hypoemotionality are indistinguishable from those of patients with "visual derealisation". There is also a phenomenological overlap between "asomatognosia" and the symptom of "body alienation", which is a central feature of depersonalisation. CONCLUSIONS: Phenomenological similarities between visual hypoemotionality and DR suggest that a disruption of the process by means of which perception becomes emotionally coloured may be an underlying mechanism in both conditions. Likewise, phenomenological overlaps with asomatognosia suggest that DP might result from parietal mechanisms disrupting the experience of body ownership and agency. These findings give validity to the notion that DP and DR may have distinct neurobiological mechanisms.

Adult↗
PubMed2001

Depersonalization disorder: thinking without feeling.

Patients with depersonalization disorder (DP) experience a detachment from their own senses and surrounding events, as if they were outside observers. A particularly common symptom is emotional detachment from the surroundings. Using functional magnetic resonance imaging (fMRI), we compared neural responses to emotionally salient stimuli in DP patients, and in psychiatric and healthy control subjects. Six patients with DP, 10 with obsessive-compulsive disorder (OCD), and six volunteers were scanned whilst viewing standardized pictures of aversive and neutral scenes, matched for visual complexity. Pictures were then rated for emotional content. Both control groups rated aversive pictures as much more emotive, and demonstrated in response to these scenes significantly greater activation in regions important for disgust perception, the insula and occipito-temporal cortex, than DP patients (covarying for age, years of education and total extent of brain activation). In DP patients, aversive scenes activated the right ventral prefrontal cortex. The insula was activated only by neutral scenes in this group. Our findings indicate that a core phenomenon of depersonalization--absent subjective experience of emotion--is associated with reduced neural responses in emotion-sensitive regions, and increased responses in regions associated with emotion regulation.

Adult↗
PubMed2001

Basal activity of the hypothalamic-pituitary-adrenal axis in patients with depersonalization disorder.

Depersonalisation disorder may occur during severe anxiety or following a traumatic event, suggesting a possible role of stress hormones. This study investigated basal activity of the hypothalamic-pituitary-adrenal (HPA) axis in patients with depersonalisation disorder. Salivary cortisol levels were measured at four time points over 12 h in patients with depersonalisation disorder (N=13), major depressive disorder (MDD, N=14) and healthy controls (N=13). Beck Depression Inventory scores were significantly higher in depersonalised subjects than controls, while MDD subjects demonstrated higher scores than both groups. Basal cortisol levels of depersonalised subjects were significantly lower than those of MDD subjects but not healthy controls. These results point to reduced basal activity of the HPA axis in depersonalisation disorder. This pilot study supports the distinction between depersonalisation disorder and major depressive disorder which should be examined in a larger sample.

Adult↗
PubMed2001

Effects of ispaghula husk and guar gum on postprandial glucose and insulin concentrations in healthy subjects.

OBJECTIVE: The aim of this study was to evaluate, under the same experimental conditions and in the same subjects, the effects of ispaghula husk and guar gum on postprandial glucose and insulin concentrations in healthy female subjects. DESIGN: An oral glucose load with and without fiber was administered in the morning after an overnight fast. The study of the fiber effect was planned according to a randomized and cross-over design. SETTING: The study was performed at the Department of Pharmacology, Toxicology and Nursing at the University of León (Spain). SUBJECTS: Ten healthy female volunteers aged 30-48 y with normal body mass indices participated in this study. RESULTS: A significant decrease in mean serum insulin concentrations was observed from 30 to 90 min in the presence of both fibers. The area under the insulin curve was significantly reduced by 36.1% for ispaghula husk and 39.4% for guar gum. The area under the glucose curve was reduced by 11.1% (significant difference) for ispaghula husk and 2.6% for guar gum (no significant difference). CONCLUSIONS: According to the results obtained in this study, the administration of ispaghula husk may be beneficial due to its ability to reduce glucose postprandial concentration and especially insulin requirements. Individualization of the treatment would be advisable due to large individual variations observed in glycemic and insulinemic postprandial responses.

Adult↗
PubMed2001

Laparoscopic pancreatic surgery in patients with neuroendocrine tumours: indications and limits.

Laparoscopic pancreatic procedures are still at an evaluation stage with regard to their indications and techniques. Between January 1998 and December 2000, 13 patients with endocrine pancreatic tumours - 11 insulinomas and 2 non-functioning tumours-underwent laparoscopic surgery, laparoscopic ultrasonography being used in all the patients. Enucleation was performed in five patients. The operative time was 2-3 hours. Distal pancreatectomy was performed in six patients with insulinomas, and spleen preservation with intact splenic vessels was feasible in five. Splenectomy was necessary in one patient for technical reasons. Laparoscopic distal pancreatectomy with splenic vessel preservation was performed in two patients with a large (6 and 8 cm) non-functioning tumour. The mean operative time for all the patients undergoing distal pancreatectomy was 4 hours, ranging from 3 to 5 hours. A pancreatic fistula occurred in three patients after tumour enucleation and in two patients after distal pancreatectomy; the mean hospital stay for all patients was 5 days. Enucleation guided by laparoscopic ultrasonography thus allows safe tumour dissection and excision, laparoscopic distal pancreatectomy also being feasible and safe. Splenic salvage with splenic vessel preservation is technically possible. The laparoscopic approach allows a shorter hospital stay and an earlier return to normal activities.

Adult↗